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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
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)Alternativ titel
Analys av ICP-pulsationer och CSF-dynamik : pulsationskurvan och effekter av ändrad kroppsposition, med implikationer för idiopatisk normaltryckshydrocefalus (Svenska)
Abstract [en]

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. 

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet , 2013. , s. 79
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1613
Nyckelord [en]
Cerebrospinal fluid, CSF dynamics, Intracranial pressure, Pulse pressure, Normal pressure hydrocephalus, Posture, Predictive tests, Mathematical modelling, Magnetic resonance imaging, Infusion tests
Nationell ämneskategori
Medicinteknik
Identifikatorer
URN: urn:nbn:se:umu:diva-82784ISBN: 978-91-7459-762-2 (tryckt)OAI: oai:DiVA.org:umu-82784DiVA, id: diva2:663891
Disputation
2013-12-06, Hörsal E 04, Unod R1, Norrlands Universitetssjukhus, Umeå, 13:00 (Engelska)
Opponent
Handledare
Forskningsfinansiär
Vetenskapsrådet, 221-2011-5216Vetenskapsrådet, VR3011-2006-7551Vinnova, VR3011-2006-7551Stiftelsen för strategisk forskning (SSF), VR3011-2006-7551
Anmärkning

Forskningsfinansiär: 

European Union, ERDF: Objective 2, Northern Sweden (grant no. 158715-CMTF). 

Tillgänglig från: 2013-11-15 Skapad: 2013-11-11 Senast uppdaterad: 2021-11-01Bibliografiskt granskad
Delarbeten
1. The pulsatility curve: the relationship between mean intracranial pressure and pulsation amplitude
Öppna denna publikation i ny flik eller fönster >>The pulsatility curve: the relationship between mean intracranial pressure and pulsation amplitude
2010 (Engelska)Ingår i: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 31, nr 11, s. 1517-1528Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Nyckelord
normal pressure hydrocephalus, pulse pressure, amplitudes, cerebrospinal fluid pressure, intracranial pressure, infusion test, arterial pulsaations
Nationell ämneskategori
Medicinteknik Neurologi
Forskningsämne
neurologi
Identifikatorer
urn:nbn:se:umu:diva-37363 (URN)10.1088/0967-3334/31/11/008 (DOI)000283491900011 ()20938063 (PubMedID)2-s2.0-78149307697 (Scopus ID)
Tillgänglig från: 2010-10-29 Skapad: 2010-10-28 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
2. Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus
Öppna denna publikation i ny flik eller fönster >>Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus
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2013 (Engelska)Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, nr 7, s. 735-741Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
BMJ Publishing Group, 2013
Nationell ämneskategori
Radiologi och bildbehandling
Identifikatorer
urn:nbn:se:umu:diva-78953 (URN)10.1136/jnnp-2012-302924 (DOI)000320108200010 ()2-s2.0-84878753397 (Scopus ID)
Forskningsfinansiär
VetenskapsrådetVinnova
Anmärkning

This project was supported by the Swedish Research Council, VINNOVA, and the Swedish Foundation for Strategic Research through their common initiative: 'Biomedical engineering for improved health' grant No VR3011-2006-7551; and by the European Union through ERDF: Objective 2, Northern Sweden grant No 158715-CMTF.

Tillgänglig från: 2013-07-29 Skapad: 2013-07-29 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
3. CSF dynamic analysis of a predictive pulsatility-based infusion test for normal pressure hydrocephalus
Öppna denna publikation i ny flik eller fönster >>CSF dynamic analysis of a predictive pulsatility-based infusion test for normal pressure hydrocephalus
2014 (Engelska)Ingår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 52, nr 1, s. 75-85Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Nyckelord
Cerebrospinal fluid dynamics, Prognostic tests, Intracranial pressure, Normal pressure hydrocephalus
Nationell ämneskategori
Medicinteknik
Identifikatorer
urn:nbn:se:umu:diva-82750 (URN)10.1007/s11517-013-1110-1 (DOI)000329663200008 ()24151060 (PubMedID)2-s2.0-84896716851 (Scopus ID)
Tillgänglig från: 2013-11-08 Skapad: 2013-11-08 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
4. Postural effects on intracranial pressure: modeling and clinical evaluation
Öppna denna publikation i ny flik eller fönster >>Postural effects on intracranial pressure: modeling and clinical evaluation
2013 (Engelska)Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, nr 10, s. 1474-1480Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
American Physiological Society, 2013
Nyckelord
intracranial pressure, spinal puncture, cerebrospinal fluid pressure, hydrocephalus, normal pressure, pulse pressure waves
Nationell ämneskategori
Medicinteknik
Identifikatorer
urn:nbn:se:umu:diva-82744 (URN)10.1152/japplphysiol.00711.2013 (DOI)000327398600008 ()24052030 (PubMedID)2-s2.0-84888382669 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 221-2011-5216VINNOVA
Tillgänglig från: 2013-11-08 Skapad: 2013-11-08 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
5. Differences in cerebral blood flow and CSF flow between INPH and healthy elderly
Öppna denna publikation i ny flik eller fönster >>Differences in cerebral blood flow and CSF flow between INPH and healthy elderly
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(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

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. 

Nationell ämneskategori
Medicinteknik
Identifikatorer
urn:nbn:se:umu:diva-82783 (URN)
Tillgänglig från: 2013-11-11 Skapad: 2013-11-11 Senast uppdaterad: 2021-11-01Bibliografiskt granskad

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