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1.
  • Akbarian-Tefaghi, Ladan, et al. (författare)
  • Refining the Deep Brain Stimulation Target within the Limbic Globus Pallidus Internus for Tourette Syndrome
  • 2017
  • Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 95:4, s. 251-258
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Deep brain stimulation (DBS) in patients with severe, refractory Tourette syndrome (TS) has demonstrated promising but variable results thus far. The thalamus and anteromedial globus pallidus internus (amGPi) have been the most commonly stimulated sites within the cortico-striato thalamic circuit, but an optimal target is yet to be elucidated.OBJECTIVES: This study of 15 patients with long-term amGPi DBS for severe TS investigated whether a specific anatomical site within the amGPi correlated with optimal clinical outcome for the measures of tics, obsessive compulsive behaviour (OCB), and mood.METHODS: Validated clinical assessments were used to measure tics, OCB, quality of life, anxiety, and depression before DBS and at the latest follow-up (17-82 months). Electric field simulations were created for each patient using information on electrode location and individual stimulation parameters. A subsequent regression analysis correlated these patient-specific simulations to percentage changes in outcome measures in order to identify any significant voxels related to clinical improvement.RESULTS: A region within the ventral limbic GPi, specifically on the medial medullary lamina in the pallidum at the level of the AC-PC, was significantly associated with improved tics but not mood or OCB outcome.CONCLUSIONS: This study adds further support to the application of DBS in a tic-related network, though factors such as patient sample size and clinical heterogeneity remain as limitations and replication is required.
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3.
  • Alonso, Fabiola, 1980-, et al. (författare)
  • Comparison between intraoperative and chronic and deep brain stimulation
  • 2017
  • Konferensbidrag (refereegranskat)abstract
    • INTRODUCTIONThe success of the deep brain stimulation (DBS) therapy relies primarily in the localization of the implanted electrode, implying the need of utmost accuracy in the targeting process. Intraoperative microelectrode recording and stimulation tests are a common procedure before implanting the permanent DBS lead to determine the optimal position with a large therapeutic window where side effects are avoided and the best improvement of the symptoms is achieved. Differences in dimensions and operating modes exist between the exploration and the permanent DBS electrode which might lead to different stimulation fields, even when ideal placement is achieved. The aim of this investigation is to compare the electric field (EF) distribution around the intraoperative and the chronic electrode, assuming that both have exactly the same position.METHODS3D models of the intraoperative exploration electrode and the chronically implanted DBS lead 3389 (Medtronic Inc., USA) were developed using COMSOL 5.2 (COMSOL AB, Sweden). Patient-specific MR images were used to determine the conductive medium around the electrode. The exploration electrode and the first DBS contact were set to current and voltage respectively (0.2mA(V) - 3 mA(V) in 0.1 mA(V) steps). The intraoperative model included the grounded guide tube used to introduce the exploration electrode; for the chronic DBS model, the outer boundaries were grounded and the inactive contacts were set to floating potential considering a monopolar configuration. The localization of the exploration and the chronic electrode was set according to the planned trajectory. The EF was visualized and compared in terms of volume and extension using a fixed isocontour of 0.2 V/mm.RESULTSThe EF distribution simulated for the exploration electrode showed the influence of the parallel trajectory and the grounded guide tube. For an amplitude of e.g. 2 mA/2 V, the EF extension of the intraoperative was 0.6 mm larger than the chronic electrode at the target level; the corresponding difference in volume was 76.1 mm3.CONCLUSIONDifferences in the EF shape between the exploration and the chronic DBS electrode have been observed using patient-specific models. The larger EF extension obtained for the exploration electrode responds to its higher impedance and the use of current controlled stimulation. The presence of EF around the guide tube and the influence of the parallel trajectory require further experimental and clinical evaluation.
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4.
  • Alonso, Fabiola, et al. (författare)
  • Comparison of deep brain stimulation systems
  • 2014
  • Ingår i: Poster Presentations. - : Wiley. ; , s. 1173-1173
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: To quantitatively compare the electric field generated by voltage and current controlled deep brain stimulation systems.Background: Traditionally deep brain stimulation (DBS) systems have used voltage control however more recently, current controlled systems have been approved to treat Parkinson's disease and related movement disorders. In the endeavor of understanding the behavior of DBS systems a common approach is the use of computer models suitable to simulate the electric field, current density and other related electric parameters.Methods: 2D finite element models based on commercially available DBS systems have been built for each system: I. Model 3389, Medtronic Inc., USA for voltage control; and II. Model 6142, St Jude Medical Inc. USA for current control. The brain tissue has been simplified to homogeneous and isotropic medium. The electric settings correspond to a monopolar configuration, using one of the four contacts available as the active electrode and the outer boundary of the tissue as the reference. Three simulations were performed to mimic different stages of the leads implantation: a) an original stage where the brain tissue is considered as pure gray matter, b) an acute stage that simulates the leakage of cerebral spinal fluid immediately after the electrodes' insertion; and c) a chronic stage mimicking fibrous tissue created around the electrodes some weeks after implantation. Both systems were submitted to the same conditions using as active electrode the third contact from the tip of the lead. The comparison is based on the maximal distance reached by the isopotential of 0.2 V/mm.Results: The simulations showed that voltage controlled stimulation systems are more susceptible to changes in the electrical conductivity of the medium i.e. change over time of the tissue around the electrode. This agrees with the adjustment of the stimulation amplitude often necessary a few weeks postoperatively. Current controlled stimulation in turn, presented a linear behavior of the distance reached at different stimulation amplitudes at all stages.Conclusions: Current controlled stimulation might be a good option due to its linear behavior over time, nevertheless more studies including a more realistic brain model, different designs of DBS electrodes and different electric parameter, are needed to encourage the use of this type of systems.
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5.
  • Alonso, Fabiola, 1980-, et al. (författare)
  • Comparison of Three Deep Brain Stimulation Lead Designs under Voltage and Current Modes
  • 2015
  • Ingår i: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2. - Cham : Springer. - 9783319193861 - 9783319193878 ; , s. 1196-1199
  • Konferensbidrag (refereegranskat)abstract
    • Since the introduction of deep brain stimulation (DBS) the technique has been dominated by Medtronic sys-tems. In recent years, new DBS systems have become available for patients, and some are in clinical trials. The present study aims to evaluate three DBS leads operated in either voltage or current mode. 3D finite element method (FEM) models were built in combination with a neuron model for this purpose. The axon diameter was set to D = 5 μm and simulations performed in both voltage (0.5-5 V) and current (0.5-5 mA) mode. The evaluation was achieved based on the distance from the lead for neural activation and the electric field (EF) extension at 0.1 V/mm. The results showed that the neural activation distance agrees well between the leads with an activation distance dif-ference less than 0.5 mm. The shape of the field at the 0.1 V/mm isopotential surface in 3D is mostly spherical in shape around the activated section of the steering lead.
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6.
  • Alonso, Fabiola, et al. (författare)
  • Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems : A Simulation Study
  • 2018
  • Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome
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  • Alonso, Fabiola, 1980-, et al. (författare)
  • Influence of Virchow-Robin spaces in the Electric Field Distribution in Subthalamic Nucleus Deep Brain Stimulation
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • Objectives: Previous investigations have shown the appearance of cysts i.e. Virchow-Robin spaces (VR) in the basal ganglia and their relationship with parkinsonian symptoms [1-3]. Simulations [4]using the finite element method (FEM) suggests that VR affects the electric field around deep brain stimulation (DBS) electrodes. The aim of the study was to evaluate how the electric field is modified by the presence of cysts in the STN. Methods: The effect of cysts on the electric field around the DBS lead placed in the STN was evaluated using FEM. 3D patient-specific brain models were built with COMSOL 5.2 (COMSOL AB, Sweden) and an in-house developed software [5] to convert a T2 weighted MRI of Parkinsonian patients (ethics approval no: 2012/434-3) into electrical conductivity matrix readable by FEM software. VR was classified as CSF [6]assigning a high electrical conductivity (2.0 S/m). The stimulation amplitudes were set to the clinically programmed values. Depending on the lead used, the stimulation was set to voltage control (3389) or current control (6180, ring mode). The coordinates corresponding to the lowest (first) electrode and the third higher up in the lead, taken from the postoperative CT electrode artefact, were used to localize the leads in the brain model [7]. The electric field was visualized with a 0.2V/mm isosurface. Results: Simulations showed that the electric field distribution is affected by the cysts. The higher conductivity at these regions in the vicinity of the electrode redistributes the electric field pushing it away from the cyst. The same effect occurs regardless of the operating mode or the lead design as long as the directional lead is configured in ring mode. Conclusions: The use of patient-specific models has shown the importance of considering nuances of the patients’ anatomy in the STN. This information can be used to determine the stimulation parameter and to support the analysis of side effects induced by the stimulation. The potential advantage of directional leads can also be assessed by including in the model patient-specific data.
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9.
  • Alonso, Fabiola, et al. (författare)
  • Influence of Virchow-Robin spaces on the electric field distribution in subthalamic nucleus deep brain stimulation
  • 2021
  • Ingår i: Clinical neurology and neurosurgery. - : Elsevier. - 0303-8467 .- 1872-6968. ; 204
  • Tidskriftsartikel (refereegranskat)abstract
    • Patient MRI from DBS implantations in the subthalamic nucleus (STN) were reviewed and it was found that around 10% had Virchow-Robin spaces (VRS). Patient-specific models were developed to evaluate changes in the electric field (EF) around DBS leads. The patients (n = 7) were implanted bilaterally either with the standard voltage-controlled lead 3389 or with the directional current-controlled lead 6180. The EF distribution was evaluated by comparing simulations using patient-specific models with homogeneous models without VRS. The EF, depicted with an isocontour of 0.2 V/mm, showed a deformation in the presence of the VRS around the DBS lead. For patient-specific models, the radial extension of the EF isocontours was enlarged regardless of the operating mode or the DBS lead used. The location of the VRS in relation to the active contact and the stimulation amplitude, determined the changes in the shape and extension of the EF. It is concluded that it is important to take the patients? brain anatomy into account as the high conductivity in VRS will alter the electric field if close to the DBS lead. This can be a cause of unexpected side effects.
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10.
  • Alonso, Fabiola, 1980-, et al. (författare)
  • Influence on Deep Brain Stimulation from Lead Design, Operating Mode and Tissue Impedance Changes – A Simulation Study
  • 2015
  • Ingår i: Brain Disorders and Therapy. - Los Angeles, CA, USA : Omics Publishing Group. - 2168-975X. ; 4:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Deep brain stimulation (DBS) systems in current mode and new lead designs are recently available. To switch between DBS-systems remains complicated as clinicians may lose their reference for programming. Simulations can help increase the understanding.Objective: To quantitatively investigate the electric field (EF) around two lead designs simulated to operate in voltage and current mode under two time points following implantation.Methods: The finite element method was used to model Lead 3389 (Medtronic) and 6148 (St Jude) with homogenous surrounding grey matter and a peri-electrode space (PES) of 250 μm. The PES-impedance mimicked the acute (extracellular fluid) and chronic (fibrous tissue) time-point. Simulations at different amplitudes of voltage and current (n=236) were performed using two different contacts. Equivalent current amplitudes were extracted by matching the shape and maximum EF of the 0.2 V/mm isolevel.Results: The maximum EF extension at 0.2 V/mm varied between 2-5 mm with a small difference between the leads. In voltage mode EF increased about 1 mm at acute compared to the chronic PES. Current mode presented the opposite relationship. Equivalent EFs for lead 3389 at 3 V were found for 7 mA (acute) and 2.2 mA (chronic).Conclusions: Simulations showed a major impact on the electric field extension between postoperative time points. This may explain the clinical decisions to reprogram the amplitude weeks after implantation. Neither the EF extension nor intensity is considerably influenced by the lead design.
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11.
  • Alonso, Fabiola, et al. (författare)
  • Investigation into Deep Brain Stimulation Lead Designs : A Patient-Specific Simulation Study
  • 2016
  • Ingår i: Brain Sciences. - : MDPI. - 2076-3425. ; 6:3, s. 1-16
  • Tidskriftsartikel (refereegranskat)abstract
    • New deep brain stimulation (DBS) electrode designs offer operation in voltage and current mode and capability to steer the electric field (EF). The aim of the study was to compare the EF distributions of four DBS leads at equivalent amplitudes (3 V and 3.4 mA). Finite element method (FEM) simulations (n = 38) around cylindrical contacts (leads 3389, 6148) or equivalent contact configurations (leads 6180, SureStim1) were performed using homogeneous and patient-specific (heterogeneous) brain tissue models. Steering effects of 6180 and SureStim1 were compared with symmetric stimulation fields. To make relative comparisons between simulations, an EF isolevel of 0.2 V/mm was chosen based on neuron model simulations (n = 832) applied before EF visualization and comparisons. The simulations show that the EF distribution is largely influenced by the heterogeneity of the tissue, and the operating mode. Equivalent contact configurations result in similar EF distributions. In steering configurations, larger EF volumes were achieved in current mode using equivalent amplitudes. The methodology was demonstrated in a patient-specific simulation around the zona incerta and a “virtual” ventral intermediate nucleus target. In conclusion, lead design differences are enhanced when using patient-specific tissue models and current stimulation mode.
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12.
  • Alonso, Fabiola, 1980- (författare)
  • Models and Simulations of the Electric Field in Deep Brain Stimulation : Comparison of Lead Designs, Operating Modes and Tissue Conductivity
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Deep brain stimulation (DBS) is an established surgical therapy for movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). A thin electrode is implanted in a predefined area of the brain with the use of stereotactic neurosurgery. In the last few years new DBS electrodes and systems have been developed with possibilities for using more parameters for control of the stimulation volume.In this thesis, simulations using the finite element method (FEM) have been developed and used for investigation of the electric field (EF) extension around different types of DBS lead designs (symmetric, steering) and stimulation modes (voltage, current). The electrode surrounding was represented either with a homogeneous model or a patient-specific model based on individual preoperative magnetic resonance imaging (MRI). The EF was visualized and compared for different lead designs and operating modes.In Paper I, the EF was quantitatively investigated around two lead designs (3389 and 6148) simulated to operate in voltage and current mode under acute and chronic time points following implantation.Simulations showed a major impact on the EF extension between postoperative time points which may explain the clinical decisions to change the stimulation amplitude weeks after implantation. In Paper II, the simulations were expanded to include two leads having steering function (6180, Surestim1) and patient-specific FEM simulations in the zona incerta. It was found that both the heterogeneity of the tissue and the operating mode, influence the EF distribution and that equivalent contact configurations of the leads result in similar EF. The steering mode presented larger volumes in current mode when using equivalent amplitudes. Simulations comparing DBS and intraoperative stimulation test using a microelectrode recording (MER) system (Paper III), showed that several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution and that the DBS EF volume can cover, but also extend to, other anatomical areas.Paper IV introduces a method for an objective exploitation of intraoperative stimulation test data in order to identify the optimal implant position in the thalamus of the chronic DBS lead. Patient-specific EF simulations were related to the anatomy with the help of brain atlases and the clinical effects which were quantified by accelerometers. The first results indicate that the good clinical effect in ET is due to several structures around the ventral intermediate nucleus of the thalamus.
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13.
  • Alonso, Fabiola, 1980-, et al. (författare)
  • Neural Activation Compared to Electric Field Extension of Three DBS Lead Designs
  • 2015
  • Konferensbidrag (refereegranskat)abstract
    • SINCE the introduction of deep brain stimulation (DBS) about 20 years ago, the stimulation technique has been dominated by Medtronic DBS-system setup. In recent years, new DBS systems have become available, of which some are in clinical trials or available to patients [1]. In the present study three different lead designs are investigated via computer simulation:Medtronic 3389, St. Jude 6148 and Sapiens SureStim. The aim was to compare the neural activation distance and the electric field (EF) maximum spatial extension for each lead.A 3D finite element method model was built using COMSOL Multiphysics 4.4a (COMSOL AB, Stockholm, Sweden) to simulate the electric potential around the DBS lead. Brain tissue was modelled as a homogeneous volume of grey matter (electric conductivity of 0.09 S/m). The electrode-tissue interface was modelled with a 250μm thick peri-electrode space mimicking the fibrous tissue which covers the lead at the chronic stimulation stage (σ = 0.06S/m, equivalent to white matter electric conductivity). The stimulation amplitude was set to 1V in monopolar configuration using C1 electrode or equivalent in all cases. Each simulated electric potential distribution was exported to MatLab (The MathWorks, USA) and used as input to a cable neuron simulation.An axon cable model with 21 nodes based on the concept by Åström et al., [2] was set up in MatLab and combined with the exported field distributions. The model considered a 5 μm thick neuron, a pulse width of 60 μs and a drive potential ranging from 0.5 V to 5 V in 0.5 V steps.The SureStim lead results showed a shorter neural activation distance and EF extension. The distance to the isolevel of 0.2 V/mm is close to the neural activation distance at each stimulation amplitude, and we conclude that the electric field is a suitable predictor to visualize the stimulated regions.
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16.
  • Anderson, C., et al. (författare)
  • Changes in skin circulation after microdialysis probe insertion visualized by laser Doppler perfusion imaging
  • 1994
  • Ingår i: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 102:5, s. 807-811
  • Tidskriftsartikel (refereegranskat)abstract
    • Microdialysis makes possible in vivo estimation of endogenous and exogenous substances in the dermal extracellular space. Insertion of the microdialysis probe and its subsequent presence in the skin may affect both the reactivity of the skin test site and the measurement of target substances. Laser Doppler flowmetry is a non-invasive method for estimating cutaneous blood flow. A further development of this technique, laser Doppler perfusion imaging, has been used to study the time course of the circulatory changes caused in the area of microdialysis probe insertion. Laser Doppler perfusion imaging was performed prior to, during, and after microdialysis probe insertion in the skin of the ventral forearm in three subjects. Probe insertion caused an increase in skin blood perfusion in the whole test area. About 15 min after probe insertion, the flare, which is presumed to be of chiefly axon reflex origin, began to subside and the circulatory response could be seen to center around the site of insertion and the tip of the probe. Skin perfusion levels had returned to near normal levels within 60 min. Local anesthesia of the point of guide insertion inhibited the flare, but did not affect circulatory reactivity in the skin nearby. Both microdialysis and laser Doppler perfusion imaging seem to be promising new methods in dermatologic research.
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19.
  • Andersson, Kennet, 1979- (författare)
  • Assessment of cerebrospinal fluid system dynamics : novel infusion protocol, mathematical modelling and parameter estimation for hydrocephalus investigations
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
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20.
  • Andersson, Nina, 1976- (författare)
  • Cerebrospinal fluid infusion methods : development and validation on patients with idiopathic normal pressure hydrocephalus
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cerebrospinal fluid (CSF) infusion tests can be used to estimate the dynamic properties of the CSF system. Idiopathic normal pressure hydrocephalus (INPH) is a syndrome signified by a disturbance to the CSF system, where the cause is unknown and the diagnosis is difficult to determine. As an aid in identifying patients with INPH who will improve after shunt surgery, infusion tests are commonly used to determine the outflow conductance (Cout), or outflow resistance (Rout=1/Cout), of the CSF system. The tests are also used to determine shunt function in vivo. The general aim of this thesis was to develop and validate CSF infusion methods, to investigate the dynamics of the CSF system. The methods should be applicable to patients with INPH, to aid in the quest to further improve the diagnosis and management of this syndrome.An existing mathematical model describing the dynamics of the CSF system was further developed. The characteristics of the model were verified and the effect of expanding intracranial air on the intracranial pressure (ICP) was simulated. The simulations supported the recommendation to maintain sea-level pressure during air ambulance transportation of patients with suspected intracranial air.A recently developed infusion apparatus was evaluated, on an experimental model as well as on a patient material. The repetitiveness in estimating Cout was found to be good. A statistically significant difference was found between the repeated Cout estimations in the patient group, indicating that there might have been a small physiological change introduced during the infusion test. A parameter, ∆Cout, was proposed and evaluated. It proved to reflect the reliability of individual Cout investigations in a clinically useful way, as well as to provide easily interpreted information.An adaptive algorithm for assessment of Cout was developed and evaluated on a patient group. The new algorithm was shown to reduce the investigation time, from 60 minutes, by 14.3 ± 5.9 minutes (mean ± SD), p<0.01, without reducing the reliability of the estimated Cout below clinically relevant levels.The relationship between ICP and CSF outflow was studied in a group of patients investigated for INPH. It was found that in the range of moderate increase from baseline pressure, the assumption of a pressure independent Rout was confirmed (p=0.5). However, at larger pressure increments, the relationship had a non-linear tendency (p<0.05). This indicates that the traditional view of a pressure independent Rout might have to be questioned in the region where ICP exceeds baseline pressure too much.Infusion tests can be performed in different ways, where three main categories may be distinguished. The bolus infusion method was compared to the constant pressure and constant flow infusion methods, on an experimental model as well as on a patient material. When physiological pressure fluctuations were added to the model, significant differences were found in the determination of Cout in the range of clinical importance, i.e. low Cout (p<0.05). The finding was supported by the patient investigations, the difference was however not significant.With the application of the new methods developed in this thesis, and the increased knowledge concerning relationships between CSF dynamic parameters, the CSF infusion test was further improved with the ability to increase measurement reliability in a reduced time. This constitutes a good basis to perform a large multi-centre study with the main goal to determine the predictive value of the parameter Cout.
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21.
  • Andersson, T., et al. (författare)
  • Human in vivo cutaneous microdialysis: Estimation of histamine release in cold urticaria.
  • 1995
  • Ingår i: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; :75, s. 343-347
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel bioanalytical in vivo sampling technique, cutaneous microdialysis, was used to follow the chronology of skin histamine release in 3 patients with cold urticaria and in 2 healthy volunteers. Laser Doppler perfusion imaging was used simultaneously to monitor the skin circulatory response. Microdialysis samples were collected at 10-min intervals and analysed by radioimmunoassay technique. Fifty minutes after probe insertion, the ventral forearm skin in the area of the dialysis membrane was provoked for 5-15 min with a 25 x 40 mm ice cube covered with plastic foil. In the cold urticaria patients, an up to 80-fold increase of histamine was observed, with peak levels 20-30 min after challenge. Histamine levels then fell to reach "baseline" levels within 50 min. In the healthy subjects, the histamine increase was earlier, less pronounced and of shorter duration. Cutaneous microdialysis and laser Doppler imaging offer new possibilities for the chronological multiparameter assessment of inflammatory skin disorders in vivo.
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22.
  • Antonsson, Johan, et al. (författare)
  • Diffuse reflectance spectroscopy measurements for tissue type discrimination during deep brain stimulation
  • 2008
  • Ingår i: Journal of neural engineering. - : IOP Publishing. - 1741-2560 .- 1741-2552. ; 5:2, s. 185-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.
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23.
  • Antonsson, Johan, et al. (författare)
  • In-vivo reflection spectroscopy measurements in pig brain during stereotactic surgery
  • 2003
  • Ingår i: Biophotonics West. - : SPIE. ; , s. 242-250
  • Konferensbidrag (refereegranskat)abstract
    • Radiofrequency (RF) lesioning in the human brain is a commonsurgical therapy for relieving severe pain as well as formovement disorders such as Parkinsonia. During the procedure a smallelectrode is introduced by stereotactic means towards a target arealocalized by CT or MRI. An RF-current is applied throughthe electrode tip when positioned in the target area. Thetissue in the proximity of the tip is heated bythe current and finally coagulated.The overall aim of this studywas to improve the RF-technique and its ability to estimatelesion size by means of optical methods. Therefore, the opticaldifferences between white and gray matter, as well as lesionedand unlesioned tissue were investigated. Reflection spectroscopy measurements in therange of 450-800 nm were conducted on fully anesthetized pigsduring stereotactic RF-lesioning (n=6). Light from a tungsten lamp wasguided to the electrode tip through optical fibers, inserted alonga 2 mm in diameter monopolar RF-electrode. Measurements were performedin steps of 0-10 mm from the target in eachhemisphere towards the entry point of the skull. In thecentral gray of the porcine brain measurements were performed bothbefore and after the creation of a lesion. A totalof 55 spectra were collected during this study. Correlation totissue type was done using post-operative MR-images. The spectral signaturefor white and gray matter differs significantly for the entirespectral range of 450-800 nm. Pre- and post-lesioning reflection spectroscopyshowed the largest differences below 600 and above 620 nm,which implies that lasers within this wavelength range may beuseful for in-vivo measurements of tissue optical changes during RF-lesioning.
  •  
24.
  • Antonsson, Johan, 1973- (författare)
  • On optical methods for intracerebral measurements during stereotactic and functional neurosurgery : Experimental studies
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Radio frequency (RF) lesioning and deep brain stimulation (DBS) are the two prevailing surgical treatments for movement disorders within the field of stereotactic and functional neurosurgery. For RF-lesioning, a small volume of brain tissue is coagulated and knowledge of the lesion size and growth is of great importance for the safety and outcome of the procedure. This thesis deals with adapting the laser Doppler perfusion monitoring (LDPM) technique for measurements in brain tissue during RF-lesioning. The relation between LDPM signal changes and developed lesion size was investigated. LDPM measurements were evaluated both in vitro (albumin protein solution) and in vivo in the porcine brain during RF-lesioning corresponding to a bilateral thalamotomy in man. The investigated signals from the LDPI measurements can be used for following the lesioning time course and to detect if a lesion was created, both in vitro and in the animal model. For the albumin model, both the total backscattered light intensity and the perfusion signal can be used as markers for estimating the final coagulation size, while in the animal model this conclusion was not statistical verified.Independent on surgical method, RF-lesioning or DBS, intracerebral guidance is an important aspect within stereotactic and functional neurosurgery. To increase the accuracy and precision of reaching the correct target, different methods for intracerebral guidance exist, such as microelectrode recording and impedance methods. In this thesis, the possibility of developing an optical intracerebral guidance method has been investigated. Diffuse reflectance spectroscopy served as technology and all measurements were performed stereotactically in both porcine and human brain. Measurements of white and gray matter showed large differences, with higher reflectivity for white brain matter, both in porcine and in human brain. For the human measurements during DBS-implants, large differences between white matter and functional targets were found. Additionally, differences between native and lesioned porcine brain matter were detected. Both studies support the idea of using diffuse reflectance spectroscopy for developing an intracerebral guidance method.
  •  
25.
  • Antonsson, Johan, et al. (författare)
  • Optical measurements during experimental stereotactic radiofrequency lesioning
  • 2006
  • Ingår i: Stereotactic and Functional Neurosurgery. - : S. Karger. - 1011-6125 .- 1423-0372. ; 84:2-3, s. 118-124
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate in vivo a laser Doppler measurement system in porcine brain tissue during thermal lesioning. A 2-mm monopolar radiofrequency lesioning electrode was equipped with optical fibers in order to monitor the lesioning procedure. Laser Doppler and backscattered light intensity signals were measured along the electrode trajectory and during bilateral lesioning in the central gray (70, 80 and 90°C, n = 14). The time course of the coagulation process could be followed by optical recordings. Two separate groups of tissue were identified from the intensity signals. The changes in the perfusion levels in both groups displayed significant changes (p < 0.05, n = 48) at all temperature settings, while backscattered light intensity was significant for only one group at the different temperatures (p < 0.05, n = 39). These results indicate that optical measurements correlate with lesion development in vivo. The study also indicates that it is possible to follow the lesioning process intra-operatively.
  •  
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