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Assessment of cerebrospinal fluid system dynamics: novel infusion protocol, mathematical modelling and parameter estimation for hydrocephalus investigations
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
2011 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Patients with idiopathic normal pressure hydrocephalus (INPH) have a disturbance in the cerebrospinal fluid (CSF) system. The treatment is neurosurgical – a shunt is placed in the CSF system. The infusion test is used to assess CSF system dynamics and to aid in the selection of patients that will benefit from shunt surgery. The infusion test can be divided into three parts: a mathematical model, an infusion protocol and a parameter estimation method. A non-linear differential equation is used to mathematically describe the CSF system, where two important parameters are the outflow conductance (Cout) and the Pressure Volume Index (PVI). These are used both for clinical and research purposes. The analysis methods for the non-linear CSF system have limited the infusion protocols of presently used infusion investigations. They come with disadvantages such as long investigation time, no estimation of PVI and no measure of the reliability of the estimates.

The aim of this dissertation was to develop and evaluate novel methods for infusion protocols, mathematical modelling and parameter estimation methods for assessment of CSF system dynamics.

The infusion protocols and parameter estimation methods in current use, constant pressure infusion (CPI), constant infusion and bolus infusion, were investigated. The estimates of Cout were compared, both on an experimental set-up and on 20 INPH patients. The results showed that the bolus method produced a significantly higher Cout than the other methods. The study suggested a method with continuous infusion for estimating Cout and emphasized that standardization of Cout measurement is necessary.

The non-linear model of the CSF system was further developed. The ability to model physiological variations that affect the CSF system was incorporated into the model and it was transformed into a linear time-invariant system. This enabled the use of methods developed for identification of such systems. The underlying model for CSF absorption was discussed and the effect of baseline resting pressure (Pr) in the analysis on the estimation of Cout was explored using two different analyses, with and without Pr.

A novel infusion protocol with an oscillating pressure pattern was introduced. This protocol was theoretically better suited for the CSF system characteristics. Three new parameter estimation methods were developed. The adaptive observer was developed from the original non-linear model of the CSF system and estimated Cout in real time. The prediction error method (PEM) and the robust simulation error (RSE) method were based on the transformed linear system, and they estimated both Cout and PVI with confidence intervals in real time. Both the oscillating pressure pattern and the reference CPI protocol were performed on an experimental set-up of the CSF system and on 47 hydrocephalus patients. The parameter estimation methods were applied to the data, and the RSE method produced estimates of Cout that were in good agreement with the reference method and allowed for an individualized and considerably reduced investigation time.

In summary, current methods have been investigated and a novel approach for assessment of CSF system dynamics has been presented. The Oscillating Pressure Infusion method, which includes a new infusion protocol, a further developed mathematical model and new parameter estimation methods has resulted in an improved way to perform infusion investigations and should be used when assessing CSF system dynamics. The advantages of the new approach are the pressure-regulated infusion protocol, simultaneous estimation of Cout and PVI and estimates of reliability that allow for an individualized investigation time.

sted, utgiver, år, opplag, sider
Umeå: Umeå university , 2011. , s. 50
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1413
Emneord [sv]
Medicinsk teknik, hydrocefalus, infusionstest, utflödeskonduktans, systemidentifiering
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-42383ISBN: 978-91-7459-175-0 (tryckt)OAI: oai:DiVA.org:umu-42383DiVA, id: diva2:409528
Disputas
2011-05-06, Bergasalen, by 27, Umeå universitetssjukhus, Umeå, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2011-04-13 Laget: 2011-04-07 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Delarbeid
1. Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance
Åpne denne publikasjonen i ny fane eller vindu >>Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance
Vise andre…
2010 (engelsk)Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 113, nr 6, s. 1294-1303Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Object There are several infusion methods available to estimate the outflow conductance (Cout) or outflow resistance (Rout = 1/Cout) of the CSF system. It has been stated that for unknown reasons, the bolus infusion method estimates a higher Cout than steady-state infusion methods. The aim of this study was to compare different infusion methods for estimation of Cout.

Methods The following 3 different infusion methods were used: the bolus infusion method (Cout bol); the constant flow infusion method, both static (Cout stat) and dynamic (Cout dyn) analyses; and the constant pressure infusion method (Cout cpi). Repeated investigations were performed on an experimental model with well-known characteristics, with and without physiological pressure variations (B-waves, breathing, and so on). All 3 methods were also performed in a randomized order during the same investigation in 20 patients with probable or possible idiopathic normal-pressure hydrocephalus; 6 of these patients had a shunt and 14 did not.

Results Without the presence of physiological pressure variations, the concordance in the experimental model was good between all methods. When they were added, the repeatability was better for the steady-state methods and a significantly higher Cout was found with the bolus method in the region of clinically relevant Cout (p < 0.05). The visual fit for the bolus infusion was dependent on subjective assessment by the operator. This experimental finding was confirmed by the clinical results, where significant differences were found in the investigations in patients without shunts between Cout of the visual bolus method and Cout stat, Cout dyn, and Cout cpi (4.58, 4.18, and 6.12 μl/[second × kPa], respectively).

Conclusions This study emphasized the necessity for standardization of Cout measurements. An experienced operator could partly compensate for difficulties in correctly estimating the pressure parameters for the bolus infusion method, but for the general user this study suggests a steady-state method for estimating Cout.

sted, utgiver, år, opplag, sider
American Association of Neurological Surgeons, 2010
Emneord
normal-pressure hydrocephalus; steady-state infusion; intracranial-pressure; csf outflow; resistance; system; shunt; management; diagnosis; dementia
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-2577 (URN)10.3171/2010.8.JNS10157 (DOI)000284565500034 ()
Merknad

Publicerades i Nina Anderssons (=Nina Sundströms) avhandling som ett manuskript med titel:

Does the cerebrospinal fluid outflow conductance determined by steady state infusion methods differ from that of the bolus infusion method?

Tilgjengelig fra: 2008-09-02 Laget: 2008-09-02 Sist oppdatert: 2018-06-09bibliografisk kontrollert
2. Assessment of cerebrospinal fluid outflow conductance using an adaptive observer-experimental and clinical evaluation
Åpne denne publikasjonen i ny fane eller vindu >>Assessment of cerebrospinal fluid outflow conductance using an adaptive observer-experimental and clinical evaluation
Vise andre…
2007 (engelsk)Inngår i: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 28, nr 11, s. 1355-1368Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Idiopathic normal pressure hydrocephalus (INPH) patients have a disturbance in the dynamics of the cerebrospinal fluid (CSF) system. The outflow conductance, C, of the CSF system has been suggested to be prognostic for positive outcome after treatment with a CSF shunt. All current methods for estimation of C have drawbacks; these include lack of information on the accuracy and relatively long investigation times. Thus, there is a need for improved methods. To accomplish this, the theoretical framework for a new adaptive observer (OBS) was developed which provides real-time estimation of C. The aim of this study was to evaluate the OBS method and to compare it with the constant pressure infusion (CPI) method. The OBS method was applied to data from infusion investigations performed with the CPI method. These consisted of repeated measurements on an experimental set-up and 30 patients with suspected INPH. There was no significant difference in C between the CPI and the OBS method for the experimental set-up. For the patients there was a significant difference, −0.84 ± 1.25 µl (s kPa)−1, mean ± SD (paired sample t-test, p < 0.05). However, such a difference is within clinically acceptable limits. This encourages further development of this new real-time approach for estimation of the outflow conductance.

Emneord
Normal pressure hydrocephalus, outflow conductance, adaptive observer, real-time estimation
Identifikatorer
urn:nbn:se:umu:diva-17754 (URN)10.1088/0967-3334/28/11/003 (DOI)17978420 (PubMedID)
Tilgjengelig fra: 2008-10-16 Laget: 2008-10-16 Sist oppdatert: 2018-06-09bibliografisk kontrollert
3. Real-time estimation of cerebrospinal fluid system parameters via oscillating pressure infusion
Åpne denne publikasjonen i ny fane eller vindu >>Real-time estimation of cerebrospinal fluid system parameters via oscillating pressure infusion
2010 (engelsk)Inngår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 48, nr 11, s. 1123-1131Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Hydrocephalus is related to a disturbed cerebrospinal fluid (CSF) system. For diagnosis, lumbar infusion test are performed to estimate outflow conductance, C (out), and pressure volume index, PVI, of the CSF system. Infusion patterns and analysis methods used in current clinical practice are not optimized. Minimizing the investigation time with sufficient accuracy is of major clinical relevance. The aim of this study was to propose and experimentally evaluate a new method, the oscillating pressure infusion (OPI). The non-linear model of the CSF system was transformed into a linear time invariant system. Using an oscillating pressure pattern and linear system identification methods, C (out) and PVI with confidence intervals, were estimated in real-time. Forty-two OPI and constant pressure infusion (CPI) investigations were performed on an experimental CSF system, designed with PVI = 25.5 ml and variable C (out). The ARX model robustly estimated C (out) (mean C (out,OPI) - C (out,CPI) = 0.08 μl/(s kPa), n = 42, P = 0.68). The Box-Jenkins model proved most reliable for PVI (23.7 ± 2.0 ml, n = 42). The OPI method, with its oscillating pressure pattern and new parameter estimation methods, efficiently estimated C (out) and PVI as well as their confidence intervals in real-time. The results from this experimental study show potential for the OPI method and supports further evaluation in a clinical setting.

sted, utgiver, år, opplag, sider
Springer, 2010
Emneord
normal pressure hydrocephalus, system identification, outflow resistance, outflow conductance, intracranial pressure, infusion test
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-36898 (URN)10.1007/s11517-010-0670-6 (DOI)000282830000007 ()20690044 (PubMedID)
Tilgjengelig fra: 2010-10-13 Laget: 2010-10-13 Sist oppdatert: 2018-06-08bibliografisk kontrollert
4. Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance
Åpne denne publikasjonen i ny fane eller vindu >>Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance
2011 (engelsk)Inngår i: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 8, nr 1, s. 15-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout) or its reciprocal the outflow resistance, (Rout) with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Pr had on the results.

METHODS: Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3+/-10.8 years (mean +/-SD). The analysis was performed without (Cexcl Pr) and with (Cincl Pr) Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p<0.05 considered significant).

RESULTS: Mean Cout for the 63 patients was: Cexcl Pr = 7.0+/-4.0 (mean +/-SD) ul/(s kPa) and Cincl Pr = 9.1+/-4.3 ul/(s kPa) and Rout was 19.0+/-9.2 and 17.7+/-11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r=0.79, n=63, p<0.01). The difference, DeltaCout, -2.1+/-2.7 ul/(s kPa) between methods was significant (p<0.01) and DeltaRout was 1.2 +/- 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between DeltaCout and Cout.

CONCLUSIONS: The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout as possible causes for the deviation from the CSF absorption model seen in some patients.

Identifikatorer
urn:nbn:se:umu:diva-40919 (URN)10.1186/2045-8118-8-15 (DOI)21385334 (PubMedID)
Tilgjengelig fra: 2011-03-14 Laget: 2011-03-14 Sist oppdatert: 2018-06-08bibliografisk kontrollert
5. Novel infusion method for measurement of CSF dynamics
Åpne denne publikasjonen i ny fane eller vindu >>Novel infusion method for measurement of CSF dynamics
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Identifikatorer
urn:nbn:se:umu:diva-42394 (URN)
Tilgjengelig fra: 2011-04-08 Laget: 2011-04-07 Sist oppdatert: 2018-06-08bibliografisk kontrollert

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