| 1. |
- Behrens, Anders, et al.
(författare)
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Are intracranial pressure wave amplitudes measurable through lumbar puncture?
- 2013
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 127:4, s. 233-241
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.
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| 2. |
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| 3. |
- Birnefeld, Johan, et al.
(författare)
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Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol : a trial in healthy volunteers
- 2024
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Ingår i: Anesthesiology. - : Wolters Kluwer. - 0003-3022 .- 1528-1175. ; 140:4, s. 669-678
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Birnefeld, Johan, 1989-
(författare)
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Cerebral hemodynamics in stroke, cerebral small vessel disease and pharmacological interventions : a 4D flow MRI study
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 5. |
- Björnfot, Cecilia, et al.
(författare)
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Assessing cerebral arterial pulse wave velocity using 4D flow MRI
- 2021
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 41:10, s. 2769-2777
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Tidskriftsartikel (refereegranskat)abstract
- Intracranial arterial stiffening is a potential early marker of emerging cerebrovascular dysfunction and could be mechanistically involved in disease processes detrimental to brain function via several pathways. A prominent consequence of arterial wall stiffening is the increased velocity at which the systolic pressure pulse wave propagates through the vasculature. Previous non-invasive measurements of the pulse wave propagation have been performed on the aorta or extracranial arteries with results linking increased pulse wave velocity to brain pathology. However, there is a lack of intracranial “target-organ” measurements. Here we present a 4D flow MRI method to estimate pulse wave velocity in the intracranial vascular tree. The method utilizes the full detectable branching structure of the cerebral vascular tree in an optimization framework that exploits small temporal shifts that exists between waveforms sampled at varying depths in the vasculature. The method is shown to be stable in an internal consistency test, and of sufficient sensitivity to robustly detect age-related increases in intracranial pulse wave velocity.
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| 6. |
- Björnfot, Cecilia, et al.
(författare)
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Eklund, Anders, et al.
(författare)
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The Pressure Difference between Eye and Brain Changes with Posture
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 80:2, s. 269-276
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma.
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| 8. |
- Farahmand, Dan, et al.
(författare)
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Intracranial pressure in hydrocephalus: impact of shunt adjustments and body positions
- 2015
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 86:2, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between intracranial pressure (ICP) and different shunt valve opening pressures in relation to body positions is fundamental for understanding the physiological function of the shunt. Objective To analyse the ICP and ICP wave amplitude (AMP) at different shunt settings and body positions in patients with hydrocephalus. Methods In this prospective study 15 patients with communicating hydrocephalus were implanted with a ligated adjustable ventriculoperitoneal shunt. They also received a portable intraparenchymatous ICP-monitoring device. Postoperative ICP and AMP were recorded with the patients in three different body positions (supine, sitting and walking) and with the shunt ligated and open at high, medium and low valve settings. In each patient 12 10 min segments were coded, blinded and analysed for mean ICP and mean AMP using an automated computer algorithm. Results Mean ICP and mean AMP were lower at all three valve settings compared with the ligated shunt state (p<0.001). Overall, when compared with the supine position, mean ICP was 11.5 +/- 1.1 (mean +/- SD) mm Hg lower when sitting and 10.5 +/- 1.1 mm Hg lower when walking (p<0.001). Mean ICP was overall 1.1 mm Hg higher (p=0.042) when walking compared with sitting. The maximal adjustability difference (highest vs lowest valve setting) was 4.4 mm Hg. Conclusions Changing from a supine to an upright position reduced ICP while AMP only increased at trend level. Lowering of the shunt valve opening pressure decreased ICP and AMP but the difference in mean ICP in vivo between the highest and lowest opening pressures was less than half that previously observed in vitro.
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| 9. |
- Holmgren, Madelene, 1992-
(författare)
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4D flow MRI and modelling to assess cerebral arterial hemodynamics : method development and evaluation, with implementation in patients with symptomatic carotid stenosis
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Blood flow measurements are important for understanding the development of cerebrovascular diseases. With 4D flow magnetic resonance imaging (4D flow MRI), simultaneous velocity measurements are obtained in all cerebral arteries in a scan of about ten minutes. However, 4D flow MRI is a relatively new technique. For usefulness in both clinics and research, detailed knowledge is needed about its accuracy and precision for flow quantification. In patients with stroke or transient ischemic attack (TIA) from a symptomatic carotid stenosis, the stenosis may generate a difference in blood pressure and flow between the left and right cerebral hemispheres. Such a hemispheric pressure difference could be an early marker of to what extent a stenosis is affecting cerebral hemodynamics, which could be useful in the planning of carotid surgery. The overall aim of the thesis was to determine the accuracy of 4D flow MRI to measure cerebral arterial blood flow, and to develop and evaluate an approach combining 4D flow MRI and computational fluid dynamics (CFD) to characterize the cerebral arterial hemodynamics, with implementation in patients with symptomatic carotid stenosis. The thesis is based on four papers, investigating two cohorts.The first cohort consisted of 35 elderly volunteers (mean age 79 years) and was studied in paper I-II. Blood flow rates were measured in nine cerebral arteries with 4D flow MRI and 2D phase-contrast MRI as reference. Three different flow quantification methods for 4D flow MRI were evaluated and optimized: one clustering approach and two threshold-based methods. The proposed new method, based on a locally adapted threshold, outperformed the previously suggested methods in flow rate quantification. For the clustering method, flow rates were systematically underestimated. 4D flow MRI was also evaluated to assess different arterial pulsatility measures, and a Windkessel model was used to estimate reference values for cerebrovascular resistance and cerebral arterial compliance in elderly.The second cohort consisted of 28 stroke and TIA patients (mean age 73 years) with symptomatic carotid stenosis and was studied in paper III-IV. With 4D flow MRI and CFD, the preoperative hemispheric pressure laterality was quantified in the patients. The pressure laterality was compared to hemispheric flow lateralities. Estimating the hemispheric pressure laterality was a promising physiological biomarker for grading the cerebral arterial hemodynamic disturbances in patients with symptomatic carotid stenosis. A CFD model was also developed to predict carotid stump pressure, i.e., the important pressure measured in the clamped carotid artery during surgical removal of the stenosis. The predicted stump pressures were correlated with the pressures measured during surgery. Stump pressure prediction was promising and could be a potential tool in the preoperative planning in order to avoid hypoperfusion during surgery. In summary, post-processing methods were successfully developed and evaluated for accurate assessment of mean and pulsatile cerebral blood flow rates with 4D flow MRI. Thereby, this thesis provided knowledge about possibilities and limitations of how 4D flow MRI can be used with respect to cerebral arterial blood flow rate assessment. By contributing with models combining 4D flow MRI and CFD, specifically developed for analysis of pressure distributions in cerebral arteries, novel methods were proposed for assessing patients with symptomatic carotid stenosis in the planning of carotid surgery.
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| 10. |
- Holmlund, Petter, et al.
(författare)
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Can pulsatile CSF flow across the cerebral aqueduct cause ventriculomegaly? : A prospective study of patients with communicating hydrocephalus.
- 2019
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of detectable cerebrospinal fluid (CSF) outflow obstructions and often with increased CSF pulsatility measured in the cerebral aqueduct (CA). We hypothesize that the cardiac-related pulsatile flow over the CA, with fast systolic outflow and slow diastolic inflow, can generate net pressure effects that could source the ventriculomegaly in these patients. This would require a non-zero cardiac cycle averaged net pressure difference (ΔPnet) over the CA, with higher average pressure in the lateral and third ventricles.Methods: We tested the hypothesis by calculating ΔPnet across the CA using computational fluid dynamics based on prospectively collected high-resolution structural (FIESTA-C, resolution 0.39 × 0.39 × 0.3 mm3) and velocimetric (2D-PCMRI, in-plane resolution 0.35 × 0.35 mm2) MRI-data from 30 patients investigated for communicating hydrocephalus.Results: The ΔPnet due to CSF pulsations was non-zero for the study group (p = 0.03) with a magnitude of 0.2 ± 0.4 Pa (0.001 ± 0.003 mmHg), with higher pressure in the third ventricle. The maximum pressure difference over the cardiac cycle ΔPmax was 20.3 ± 11.8 Pa and occurred during systole. A generalized linear model verified an association between ΔPnet and CA cross-sectional area (p = 0.01) and flow asymmetry, described by the ratio of maximum inflow/outflow (p = 0.04), but not for aqueductal stroke volume (p = 0.35).Conclusions: The results supported the hypothesis with respect to the direction of ΔPnet, although the magnitude was low. Thus, although the pulsations may generate a pressure difference across the CA it is likely too small to explain the ventriculomegaly in communicating hydrocephalus.
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| 11. |
- Holmlund, Petter, 1988-
(författare)
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Fluid dynamic principles for analysis of intracranial pressure control : application towards space medicine and hydrocephalus
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intracranial pressure (ICP) is an important component of the fluid dynamic environment of the brain and plays a central role with regards to the maintenance of normal cerebral blood flow and neuronal function. However, many regulatory mechanisms controlling the ICP are still poorly understood. One major gap in knowledge in this regard is the mechanism behind the postural/gravitational control of ICP. This is partly due to the fact that most ICP investigations are performed with the patients in a supine or recumbent position. Since most people spend 16 hours a day in an upright position, understanding these mechanics is highly motivated. Also spurring research on this topic is the increasing number of reports of the spaceflight-associated neuro-ocular syndrome (SANS) found in astronauts after prolonged exposure to weightlessness (i.e. microgravity), where evidence suggests that a disrupted balance between ICP and intraocular pressure (IOP) may be an underlying cause. Understanding how ICP is regulated with respect to posture could therefore provide important insight into the alterations introduced by microgravity, where postural effects are removed, and how to improve the safety of astronauts who are susceptible to this syndrome. Here on earth, disturbances in the ICP or cerebrospinal fluid (CSF) dynamics are associated with the development of chronic neurological diseases. One particular disease of interest is communicating hydrocephalus, where the cerebral ventricles are enlarged despite the absence of macroscopic CSF flow obstructions. A common finding in these patients is that of altered pulsatile flow in the CSF. The overall aim of this thesis was to utilize fluid dynamic principles to describe and validate potential regulatory mechanisms behind postural changes in ICP and causes of ventriculomegaly. The thesis is based on four scientific papers (paper I—IV).A postural dependency of the IOP-ICP pressure difference was verified by simultaneous measurements of ICP (assessed through lumbar puncture) and IOP (measured with an Applanation Resonance Tonometer) (paper I). Based on these measurements, a 24-hour average of the IOP-ICP pressure difference at the level of the eye was estimated for the state of microgravity, predicting a reduced pressure difference in space compared with that on earth.A hypothesis where postural changes in ICP are described by hydrostatic effects in the venous system, and where these effects are altered by the collapse of the internal jugular veins (IJVs) in more upright positions, was evaluated (paper II and III). Using ultrasound data, it was shown that the venous hydrostatic pressure gradient was balanced by viscous pressure losses in the collapsed IJVs to uphold a near atmospheric pressure at the level of the neck in the upright posture (paper II). A full evaluation of the hypothesis was then performed, based on simultaneous assessment of ICP, central venous pressure (through a PICC-line) and venous collapse in 7 postures of upper-body tilt in healthy volunteers (paper III).The proposed description could accurately predict the general changes seen in the measured ICP for all investigated postures (mean difference: -0.03±2.7 mmHg or -4.0±360 Pa).Pulsatile CSF flow-induced pressure differences between the ventricles and subarachnoid space were evaluated as a source for ventriculomegaly in communicating hydrocephalus (paper IV). The pressure distributions resulting from the pulsatile CSF flow were calculated using computational fluid dynamics based on MRI data. The estimated pressures revealed a net pressure difference (mean: 0.001±0.003 mmHg or 0.2±0.4 Pa, p=0.03) between the ventricles and the subarachnoid space, over the cardiac cycle, with higher pressure in the third and lateral ventricles.In conclusion, the results of this thesis support venous hydrostatics and jugular venous collapse as key governing factors in the postural/gravitational control of ICP. Furthermore, a postural dependency of the IOP-ICP pressure difference was demonstrated, providing a potential explanation for how an imbalance between the pressure of the eye and brain can be introduced in microgravity. Computational fluid dynamic analysis revealed that the altered pulsations in communicating hydrocephalus generate a pressure gradient within the CSF system. However, the gradient was small and additional effects are probably needed to explain the ventriculomegaly in these patients.
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| 12. |
- Holmlund, Petter, et al.
(författare)
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Human jugular vein collapse in the upright posture : implications for postural intracranial pressure regulation
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.
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| 13. |
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| 14. |
- Holmlund, Petter, et al.
(författare)
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Venous collapse regulates intracranial pressure in upright body positions
- 2018
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 314:3, s. R377-R385
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Tidskriftsartikel (refereegranskat)abstract
- Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (PICC-line) and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47±10 years) in seven positions, from supine to sitting (0°-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP to predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference: -0.03±2.7 mmHg). No difference was found between predicted and measured ICP for any tilt-angle (p-values: 0.65 - 0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of the postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.
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| 15. |
- Jacobsson, Johan, et al.
(författare)
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Comparison of the CSF dynamics between patients with idiopathic normal pressure hydrocephalus and healthy volunteers
- 2019
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 131:4, s. 1018-1023
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Intracranial pressure (ICP), outflow resistance (Rout), and amplitude of cardiac-related ICP pulsations (AMPs) are established parameters to describe the CSF hydrodynamic system and are assumed, but not confirmed, to be disturbed in idiopathic normal pressure hydrocephalus (INPH). The aim of this study was to compare the CSF hydrodynamic profile between patients with INPH and healthy volunteers.METHODS: Sixty-two consecutive INPH patients (mean age 74 years) and 40 healthy volunteers (mean age 70 years) were included. Diagnosis was made by two independent neurologists who assessed patients’ history, neurological status, and MRI studies. A CSF dynamic investigation through the lumbar route was performed: ICP and other CSF dynamic variables were blinded to the neurologists during the diagnostic process and were not used for establishing the diagnosis of INPH.RESULTS: Rout was significantly higher in INPH (Rout 17.1 vs 11.1; p < 0.001), though a substantial number of INPH subjects had normal Rout. There were no differences between INPH patients and controls regarding ICP (mean 11.5 mm Hg). At resting pressure, there was a trend that AMP in INPH was increased (2.4 vs 2.0 mm Hg; p = 0.109). The relationship between AMP and ICP was that they shared the same slope, but the curve was significantly shifted to the left for INPH (reduced P0 [p < 0.05]; i.e., higher AMP for the same ICP).CONCLUSIONS: This study established that the CSF dynamic profile of INPH deviates from that of healthy volunteers and that INPH should thus be regarded as a disease in which intracranial hydrodynamics are part of the pathophysiology.Clinical trial registration no.: NCT01188382 (clinicaltrials.gov)
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| 16. |
- Jóhannesson, Gauti, 1979-, et al.
(författare)
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Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension
- 2020
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 61:12
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.METHODS: Subjects with untreated ocular hypertension (n = 30; mean age 67 +/- 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.RESULTS: The mean OA blood flow rate before and after treatment was 12.4 +/- 4.4 and 12.4 +/- 4.6 mL/min in the treated eye (mean +/- SD; P = 0.92) and 13.5 +/- 5.2 and 13.4 +/- 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 +/- 3.1 vs.-0.1 +/- 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 +/- 3.1 mm Hg in the treated eye (P < 0.01).CONCLUSIONS: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.
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| 17. |
- Kaipainen, Aku L, et al.
(författare)
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Cerebrospinal fluid dynamics in idiopathic intracranial hypertension : a literature review and validation of contemporary findings
- 2021
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 163:12, s. 3353-3368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort.Method: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman’s criteria, hence referred to as symptomatic controls.Results: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05).Conclusions: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.
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| 18. |
- Kristiansen, Martin, et al.
(författare)
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Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls
- 2018
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Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 59:9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.
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| 19. |
- Kristiansen, Martin, et al.
(författare)
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Feasibility of MRI to assess differences in ophthalmic artery blood flow rate in normal tension glaucoma and healthy controls
- 2021
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Ingår i: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 99:5, s. e679-e685
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine feasibility of phase-contrast magnetic resonance imaging (PCMRI) and to assess blood flow rate in the ophthalmic artery (OA) in patients with normal tension glaucoma (NTG) compared with healthy controls.Methods: Sixteen patients with treated NTG and 16 age- and sex-matched healthy controls underwent PCMRI using a 3-Tesla scanner and ophthalmological examinations. OA blood flow rate was measured using a 2D PCMRI sequence with a spatial resolution of 0.35 mm(2).Results: The blood flow rate in the NTG group was 9.6 +/- 3.9 ml/min [mean +/- SD] compared with 11.9 +/- 4.8 ml/min in the control group. Resistance Index (RI) and Pulsatility Index (PI) were 0.73 +/- 0.08 and 1.36 +/- 0.29, respectively, in the NTG group and 0.68 +/- 0.13 and 1.22 +/- 0.40, respectively, in the healthy group. The mean visual field index (VFI) was 46% +/- 25 for the worse NTG eyes. The measured differences observed between the NTG group and the control group in blood flow rate (p = 0.12), RI (p = 0.18) and PI (p = 0.27) were non-significant.Conclusions: This case-control study, using PCMRI, showed a slight, but non-significant, reduction in OA blood flow rate in the NTG patients compared with the healthy controls. These results indicate that blood flow may be of importance in the pathogenesis of NTG. Considering that only a limited portion of the total OA blood flow supplies the ocular system and the large inter-individual differences, a larger study or more advanced PCMRI technique might give the answer.
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| 20. |
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| 21. |
- Lindén, Christina, et al.
(författare)
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Normal-Tension Glaucoma Has Normal Intracranial Pressure : A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions
- 2018
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Ingår i: Ophthalmology. - : Elsevier BV. - 0161-6420 .- 1549-4713. ; 125:3, s. 361-368
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To test the hypothesis that normal-tension glaucoma (NTG) is caused by an increased pressure difference across the lamina cribrosa (LC) related to a low intracranial pressure (ICP).DESIGN: Prospective case-control study.PARTICIPANTS: Thirteen NTG patients (9 women; median 71 [range: 56-83] years) were recruited for investigation with the same protocol as 11 healthy volunteers (8 women; 47 [30-59] years). A larger control group (n = 51; 30 women; 68 [30-81] years) was used only for ICP comparison in supine position.METHODS: ICP and intraocular pressure (IOP) were simultaneously measured in supine, sitting, and 9° head-down tilt (HDT) positions. Trans-lamina cribrosa pressure difference (TLCPD) was calculated using ICP and IOP together with geometric distances estimated from magnetic resonance imaging to adjust for hydrostatic effects.MAIN OUTCOME MEASURES: ICP, IOP, and TLCPD in different body positions.RESULTS: Between NTG patients and healthy volunteers, there were no differences in ICP, IOP, or TLCPD in supine, sitting, or HDT (P ≥ 0.11), except for IOP in HDT (P = 0.04). There was no correlation between visual field defect and TLCPD, IOP, or ICP and in any body position (P ≥ 0.39). Mean ICP in supine was 10.3 mmHg (SD = 2.7) in the NTG group (n = 13) and 11.3 (2.2) mmHg in the larger control group (n = 51) (P = 0.24).CONCLUSIONS: There was no evidence of reduced ICP in NTG patients as compared with healthy controls, either in supine or in upright position. Consequently, the hypothesis that NTG is caused by an elevated TLCPD from low ICP was not supported.
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| 22. |
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| 23. |
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| 24. |
- Luciano, Mark G., et al.
(författare)
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Epidural Oscillating Cardiac-Gated Intracranial Implant Modulates Cerebral Blood Flow
- 2020
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Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 87:6, s. 1299-1310
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously reported a method and device capable of manipulating ICP pulsatility while minimally effecting mean ICP.Objective: To test the hypothesis that different modulations of the intracranial pressure (ICP) pulse waveform will have a differential effect on cerebral blood flow (CBF).Methods: Using an epidural balloon catheter attached to a cardiac-gated oscillating pump, 13 canine subjects underwent ICP waveform manipulation comparing different sequences of oscillation in successive animals. The epidural balloon was implanted unilaterally superior to the Sylvian sulcus. Subjects underwent ICP pulse augmentation, reduction and inversion protocols, directly comparing time segments of system activation and deactivation. ICP and CBF were measured bilaterally along with systemic pressure and heart rate. CBF was measured using both thermal diffusion, and laser doppler probes.Results: The activation of the cardiac-gate balloon implant resulted in an ipsilateral/contralateral ICP pulse amplitude increase with augmentation (217%/202% respectively, P < .0005) and inversion (139%/120%, P < .0005). The observed changes associated with the ICP mean values were smaller, increasing with augmentation (23%/31%, P < .0001) while decreasing with inversion (7%/11%, P = .006/.0003) and reduction (4%/5%, P < .0005). CBF increase was observed for both inversion and reduction protocols (28%/7.4%, P < .0001/P = .006 and 2.4%/1.3%, P < .0001/P = .003), but not the augmentation protocol. The change in CBF was correlated with ICP pulse amplitude and systolic peak changes and not with change in mean ICP or systemic variables (heart rate, arterial blood pressure).Conclusion: Cardiac-gated manipulation of ICP pulsatility allows the study of intracranial pulsatile dynamics and provides a potential means of altering CBF.
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| 25. |
- Luciano, Mark G., et al.
(författare)
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Novel method for dynamic control of intracranial pressure
- 2017
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Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 126:5, s. 1629-1640
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT Intracranial pressure (ICP) pulsations are generally considered a passive result of the pulsatility of blood flow. Active experimental modification of ICP pulsations would allow investigation of potential active effects on blood and CSF flow and potentially create a new platform for the treatment of acute and chronic low blood flow states as well as a method of CSF substance clearance and delivery. This study presents a novel method and device for altering the ICP waveform via cardiac-gated volume changes.METHODS The novel device used in this experiment (named Cadence) consists of a small air-filled inelastic balloon (approximately 1.0 ml) implanted into the intracranial space and connected to an external programmable pump, triggered by an R-wave detector. Balloons were implanted into the epidural space above 1 of the hemispheres of 19 canines for up to 10 hours. When activated, the balloons were programed to cyclically inflate with the cardiac cycle with variable delay, phase, and volume. The ICP response was measured in both hemispheres. Additionally, cerebral blood flow (heat diffusion and laser Doppler) was studied in 16 canines.RESULTS This system, depending on the inflation pattern of the balloon, allowed a flattening of the ICP waveform, increase in the ICP waveform amplitude, or phase shift of the wave. This occurred with small mean ICP changes, typically around ± 2 mm Hg (15%). Bilateral ICP effects were observed with activation of the device: balloon inflation at each systole increased the systolic ICP pulse (up to 16 mm Hg, 1200%) and deflation at systole decreased or even inverted the systolic ICP pulse (-0.5 to -19 mm Hg, -5% to -1600%) in a dose-(balloon volume) dependent fashion. No aphysiological or deleterious effects on systemic pressure (≤ ±10 mm Hg; 13% change in mean pressure) or cardiac rate (≤ ± 17 beats per minute; 16% change) were observed during up to 4 hours of balloon activity.CONCLUSIONS The results of these initial studies using an intracranially implanted, cardiac-gated, volume-oscillating balloon suggest the Cadence device can be used to modify ICP pulsations, without physiologically deleterious effects on mean ICP, systemic vascular effects, or brain injury. This device and technique may be used to study the role of ICP pulsatility in intracranial hemo- and hydrodynamic processes and introduces the creation of a potential platform of a cardiac-gated system for treatment of acute and chronic low blood flow states, and diseases requiring augmentation of CSF substance clearance or delivery.
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| 26. |
- Podgoršak, Anthony, et al.
(författare)
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Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model
- 2022
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously.Methods: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer’s solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated.Results: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively—showing deviations between the two estimation methods.Conclusions: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.
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| 27. |
- Qvarlander, Sara, 1982-
(författare)
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Analysis of ICP pulsatility and CSF dynamics : the pulsatility curve and effects of postural changes, with implications for idiopathic normal pressure hydrocephalus
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The volume defined by the rigid cranium is shared by the brain, blood and cerebrospinal fluid (CSF). With every heartbeat the arterial blood volume briefly increases and venous blood and CSF are forced out of the cranium, leading to pulsatility in CSF flow and intracranial pressure (ICP). Altered CSF pulsatility has been linked to idiopathic normal pressure hydrocephalus (INPH), which involves enlarged cerebral ventricles and symptoms of gait/balance disturbance, cognitive decline and urinary incontinence that may be improved by implantation of a shunt. The overall aim of this thesis was to investigate the fluid dynamics of the CSF system, with a focus on pulsatility, and how they relate to INPH pathophysiology and treatment.Mathematical modelling was applied to data from infusion tests, where the ICP response to CSF volume manipulation is measured, to analyse the relationship between mean ICP and ICP pulse amplitude (AMP) before and after shunt surgery in INPH (paper I-II). The observed relationship, designated the pulsatility curve, was found to be constant at low ICP and linear at high ICP, corresponding to a shift from constant to ICP dependent compliance (paper I). Shunt surgery did not affect the pulsatility curve, but shifted baseline ICP and AMP along the curve towards lower values. Patients who improved in gait after surgery had significantly larger AMP reduction than those who did not, while ICP reduction was similar, suggesting that improving patients had baseline ICP in the linear zone of the curve before surgery. Use of this phenomenon for outcome prediction was promising (paper II). The fluid dynamics of an empirically derived pulsatility-based predictive infusion test for INPH was also investigated, with results showing strong influence from compliance (paper III).Clinical ICP data at different body postures was used to evaluate three models describing postural effects on ICP. ICP decreased in upright positions, whereas AMP increased. The model describing the postural effects based on hydrostatic changes in the venous system, including effects of collapse of the jugular veins in the upright position, accurately predicted the measured ICP (paper IV).Cerebral blood flow and CSF flow in the aqueduct and at the cervical level was measured with phase contrast magnetic resonance imaging, and compared between healthy elderly and INPH (paper V). Cerebral blood flow and CSF flow at the cervical level were similar in INPH patients and healthy elderly, whereas aqueductal CSF flow differed significantly. The pulsatility in the aqueduct flow was increased, and there was more variation in the net flow in INPH, but the mean net flow was normal, i.e. directed from the ventricles to the subarachnoid space (paper V).In conclusion, this thesis introduced the concept of pulsatility curve analysis, and provided evidence that pulsatility and compliance are important aspects for successful shunt treatment and outcome prediction in INPH. It was further confirmed that enhanced pulsatility of aqueduct CSF flow was the most distinct effect of INPH pathophysiology on cerebral blood flow and CSF flow. A new model describing postural and hydrostatic effects on ICP was presented, and the feasibility and potential importance of measuring ICP in the upright position in INPH was demonstrated.
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| 28. |
- Qvarlander, Sara, et al.
(författare)
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Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus
- 2017
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 135:5, s. 576-584
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology.Materials and Methods: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age).Results: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays.Conclusions: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.
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| 29. |
- Qvarlander, Sara, 1982-, et al.
(författare)
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CSF dynamic analysis of a predictive pulsatility-based infusion test for normal pressure hydrocephalus
- 2014
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Ingår i: Medical and Biological Engineering and Computing. - : Springer Science and Business Media LLC. - 0140-0118 .- 1741-0444. ; 52:1, s. 75-85
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Tidskriftsartikel (refereegranskat)abstract
- Disturbed cerebrospinal fluid (CSF) dynamics are part of the pathophysiology of normal pressure hydrocephalus (NPH) and can be modified and treated with shunt surgery. This study investigated the contribution of established CSF dynamic parameters to AMPmean, a prognostic variable defined as mean amplitude of cardiac-related intracranial pressure pulsations during 10 min of lumbar constant infusion, with the aim of clarifying the physiological interpretation of the variable. AMPmean and CSF dynamic parameters were determined from infusion tests performed on 18 patients with suspected NPH. Using a mathematical model of CSF dynamics, an expression for AMPmean was derived and the influence of the different parameters was assessed. There was high correlation between modelled and measured AMPmean (r = 0.98, p < 0.01). Outflow resistance and three parameters relating to compliance were identified from the model. Correlation analysis of patient data confirmed the effect of the parameters on AMPmean (Spearman's ρ = 0.58-0.88, p < 0.05). Simulated variations of ±1 standard deviation (SD) of the parameters resulted in AMPmean changes of 0.6-2.9 SD, with the elastance coefficient showing the strongest influence. Parameters relating to compliance showed the largest contribution to AMPmean, which supports the importance of the compliance aspect of CSF dynamics for the understanding of the pathophysiology of NPH.
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| 30. |
- Qvarlander, Sara, Teknisk doktor, 1982-, et al.
(författare)
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CSF formation rate : a potential glymphatic flow parameter in hydrocephalus?
- 2024
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Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort.Methods: CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978.Results: Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135).Conclusions: The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.
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| 31. |
- Qvarlander, Sara, 1982-, et al.
(författare)
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Differences in cerebral blood flow and CSF flow between INPH and healthy elderly
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic normal pressure hydrocephalus (INPH) is linked to disturbance of the CSF circulation, though the exact nature of the disturbance is not clarified. Phase contrast magnetic resonance imaging (PC-MRI) allows for measurement of local CSF and blood flows, and has been applied in hydrocephalus to demonstrate changes in both cerebral blood flow and aqueduct CSF flow. Many of these studies have, however been based on small numbers of subjects, or poorly defined selection criteria. This study therefore aimed to confirm if cerebral blood flow and CSF flow between compartments differed between INPH subjects and healthy elderly.Forty-three healthy elderly and 22 patients diagnosed with INPH according to the INPH guidelines were investigated with PC-MRI measurements of cerebral arterial inflow (CBF) and internal jugular venous outflow, cervical CSF flow, and aqueduct CSF flow. Both net flows, pulsatile aspects of flow, and delays between flow waveforms were analysed.Pulsatility in the aqueduct flow was significantly higher in INPH than healthy elderly (aqueduct stroke volume: 189±184 vs. 86±46 ml, p<0.01). There was larger variation in aqueduct net flow in INPH (SD: 1.31 vs. 0.25 ml/min), but the mean net flow did not differ. Cerebral blood flow and internal jugular vein flow showed no significant differences between the groups, though there was a trend toward lower CBF in the diastolic phase and higher CBF pulsatility index. No differences were found in flow delays.In conclusion, cerebral in- and outflow of blood, and cervical CSF flow were similar in healthy elderly and INPH subjects. Aqueduct flow showed higher pulsatility in INPH, but there was no general reversal of the direction of aqueduct net flow.
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| 32. |
- Qvarlander, Sara, Teknisk doktor, 1982-, et al.
(författare)
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Modifying the ICP pulse wave : effects on parenchymal blood flow pulsatility
- 2023
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 134:2, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- Pulsation of the cerebral blood flow (CBF) produces intercranial pressure (ICP) waves. The aim of this study is to determine whether externally modifying ICP pulsatility alters parenchymal blood flow pulsatility. A cardiac-gated inflatable device was inserted in the lateral epidural space of 12 anesthetized canines (canis familiaris) and used to cause reduction, inversion, and augmentation of the ICP pulse. CBF in each hemisphere was measured using laser Doppler velocimetry. A significant increase in both mean CBF and its amplitude was observed for reduction as well as inversion of the ICP pulse, with larger changes observed for the inversion protocol. Significant increases in the mean CBF were also observed ipsilaterally for the augmentation protocol together with indications of reduced CBF amplitude contralaterally. External alteration of the ICP pulse thus caused significant changes in parenchymal blood flow pulsatility. The inverse relationship between the ICP and CBF amplitude suggests that the changes did not occur via modification of the intracranial Windkessel mechanism. Thus, the effects likely occurred in the low-pressure vessels, i.e., capillaries and/or venules, rather than the high-pressure arteries. Future MRI studies are however required to map and quantify the effects on global cerebral blood flow.NEW & NOTEWORTHY This study demonstrated that external modification of ICP pulsatility, using a cardiac-gated inflatable device implanted epidurally in canines, alters brain tissue blood flow pulsatility. Specifically, decreasing systolic ICP increased blood flow pulsatility in brain tissue. The results suggest that the altered CBF pulsatility is unlikely to depend on modification of the Windkessel effect on the feeding arterial system but was rather an effect directly on tissue and the lower pressure distal vessels.
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| 33. |
- Qvarlander, Sara, 1982-, et al.
(författare)
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Postural effects on intracranial pressure : modeling and clinical evaluation
- 2013
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 115:10, s. 1474-1480
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The physiological effect of posture on intracranial pressure (ICP) is not well described. This study defined and evaluated three mathematical models describing the postural effects on ICP, designed to predict ICP at different head-up tilt-angles from the supine ICP value.Methods Model I was based on a hydrostatic indifference point for the cerebrospinal fluid (CSF) system, i.e. the existence of a point in the system where pressure is independent of body position. Models II and III were based on Davson's equation for CSF absorption, which relates ICP to venous pressure, and postulated that gravitational effects within the venous system are transferred to the CSF system. Model II assumed a fully communicating venous system and model III that collapse of the jugular veins at higher tilt-angles creates two separate hydrostatic compartments. Evaluation of the models was based on ICP measurements at seven tilt-angles (0-71°)in 27 normal pressure hydrocephalus patients.Results ICP decreased with tilt-angle (ANOVA, p<0.01). The reduction was well predicted by model III (ANOVA lack-of-fit: p=0.65), which showed excellent fit against measured ICP. Neither model I nor II adequately described the reduction in ICP (ANOVA lack-of-fit: p<0.01).Conclusion Postural changes in ICP could not be predicted based on the currently accepted theory of a hydrostatic indifference point for the CSF system, but a new model combining Davson's equation for CSF absorption and hydrostatic gradients in a collapsible venous system performed well and can be useful in future research on gravity and CSF physiology.
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| 34. |
- Qvarlander, Sara, et al.
(författare)
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Pulsatility in CSF dynamics : pathophysiology of idiopathic normal pressure hydrocephalus
- 2013
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group. - 0022-3050 .- 1468-330X. ; 84:7, s. 735-741
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.Methods: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase >= 0.1 m/s.Results: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0 +/- 2.9 mm Hg; -1.1 +/- 1.5 mm Hg; p < 0.05, n = 51). Amplitude reduction was larger for gait improvers (-1.2 +/- 1.6 mm Hg, n = 42) than non-improvers (-0.2 +/- 0.5 mm Hg, n = 9) (p < 0.05) although mean ICP reduction did not differ.Conclusions: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.
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| 35. |
- Qvarlander, Sara, et al.
(författare)
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The pulsatility curve : the relationship between mean intracranial pressure and pulsation amplitude
- 2010
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Ingår i: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 31:11, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- The amplitude of cardiac-related pulsations in intracranial pressure has recently been suggested as useful for selecting patients for shunt surgery in hydrocephalus. To better understand how shunting affects these pulsations, we aim to model the relationship between mean pressure and pulsation amplitude in a wide range, including low pressures typically found after shunt surgery. Twenty-five patients with probable idiopathic normal pressure hydrocephalus were examined with lumbar constant pressure infusion investigations including drainage of cerebrospinal fluid. Mean pressure and pulsation amplitude were determined for consecutive 1.5 s intervals, starting at peak pressure (ca 35 mmHg), after infusion, continuing during spontaneous return to baseline and drainage to 0 mmHg. The amplitude versus pressure relationship revealed a linear phase at higher pressures (14-32 mmHg, lack of fit test: p = 0.79), a transitional phase and an essentially constant phase at low pressures (0-10 mmHg, slope = -0.02, lack of fit test: p = 0.88). Individual patients' baseline values were found in all three phases. The model and methodology presented in this paper can be used to preoperatively identify patients with potential for postoperative amplitude decrease and to predict how much the amplitude can be reduced.
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| 36. |
- van Osch, Matthias J. P., et al.
(författare)
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Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood
- 2024
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Ingår i: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492.
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Forskningsöversikt (refereegranskat)abstract
- Over the last decade, it has become evident that cerebrospinal fluid (CSF) plays a pivotal role in brain solute clearance through perivascular pathways and interactions between the brain and meningeal lymphatic vessels. Whereas most of this fundamental knowledge was gained from rodent models, human brain clearance imaging has provided important insights into the human system and highlighted the existence of important interspecies differences. Current gold standard techniques for human brain clearance imaging involve the injection of gadolinium-based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2 days. With both intrathecal and intravenous injections being used, which each have their own specific routes of distribution and thus clearance of contrast agent, a clear understanding of the kinetics associated with both approaches, and especially the differences between them, is needed to properly interpret the results. Because it is known that intrathecally injected contrast agent reaches the blood, albeit in small concentrations, and that similarly some of the intravenously injected agent can be detected in CSF, both pathways are connected and will, in theory, reach the same compartments. However, because of clear differences in relative enhancement patterns, both injection approaches will result in varying sensitivities for assessment of different subparts of the brain clearance system. In this opinion review article, the “EU Joint Programme – Neurodegenerative Disease Research (JPND)” consortium on human brain clearance imaging provides an overview of contrast agent pharmacokinetics in vivo following intrathecal and intravenous injections and what typical concentrations and concentration–time curves should be expected. This can be the basis for optimizing and interpreting contrast-enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.
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