Effect of infusion tests on the dynamical properties of intracranial pressure in hydrocephalus

Producción CientíficaHydrocephalus comprises a number of conditions characterised by clinical symptoms, dilated ventricles and anomalous cerebrospinal fluid (CSF) dynamics. Infusion tests (ITs) are usually performed to study CSF circulation and in the preoperatory evaluation of patients with hydrocephalus. The study of intracranial pressure (ICP) signals recorded during ITs could be useful to gain insight into the underlying pathophysiology of this condition and to further support treatment decisions. In this study, two wavelet parameters, wavelet turbulence (WT) and wavelet entropy (WE), were analysed in order to characterise the variability, irregularity and similarity in spectral content of ICP signals in hydrocephalus.Ministerio de Economía y Competitividad (TEC2014-53196-R)Junta de Castilla y León (project VA059U13

Continuous wavelet transform in the study of the time-scale properties of intracranial pressure in hydrocephalus

Producción CientíficaNormal pressure hydrocephalus (NPH) encompasses a heterogeneous group of disorders generally characterised by clinical symptoms, ventriculomegaly and anomalous cerebrospinal fluid (CSF) dynamics. Lumbar infusion tests (ITs) are frequently performed in the preoperatory evaluation of patients who show NPH features. The analysis of intracranial pressure (ICP) signals recorded during ITs could be useful to better understand the pathophysiology underlying NPH and to assist treatment decisions. In this study, 131 ICP signals recorded during ITs were analysed using two continuous wavelet transform (CWT)-derived parameters: Jensen Divergence (JD) and Spectral Flux (SF). These parameters were studied in two frequency bands, associated with different components of the signal: "(0.15 - 0.3 Hz), related to respiratory blood pressure oscillations; and # (0.67 - 2.5 Hz), related to ICP pulse waves. Statistically significant differences ( < 1.70 ∙ 10+,, Bonferroni-corrected Wilcoxon signed rank tests) in pairwise comparisons between phases of ITs were found using the mean and standard deviation of JD and SF. These differences were mainly found in #, where a lower irregularity and variability, together with less prominent time-frequency fluctuations, were found in the hypertension phase of ITs. Our results suggest that wavelet analysis could be useful for understanding CSF dynamics in NPH.This research was supported by ‘Ministerio de Economía y Competitividad’ and 'European Regional Development Fund' (FEDER) under project TEC2014-53196-R, by ‘European Commission’ and FEDER under project 'Análisis y correlación entre el genoma completo y la actividad cerebral para la ayuda en el diagnóstico de la enfermedad de Alzheimer' ('Cooperation Programme Interreg V-A Spain-Portugal POCTEP 2014-2020'), and by ‘Consejería de Educación de la Junta de Castilla y León’ and FEDER under project VA037U16

Continuous wavelet transform in the study of the time-scale properties of intracranial pressure in hydrocephalus

[EN]Normal pressure hydrocephalus (NPH) encompasses a heterogeneous group of disorders generally characterized by clinical symptoms, ventriculomegaly and anomalous cerebrospinal fluid (CSF) dynamics. Lumbar infusion tests (ITs) are frequently performed in the preoperatory evaluation of patients who show NPH features. The analysis of intracranial pressure (ICP) signals recorded during ITs could be useful to better understand the pathophysiology underlying NPH and to assist treatment decisions. In this study, 131 ICP signals recorded during ITs were analysed using two continuous wavelet transform (CWT)- derived parameters: Jensen divergence (JD) and spectral flux (SF). These parameters were studied in two frequency bands, associated with different components of the signal: B1(0.150.3 Hz), related to respiratory blood pressure oscillations; and B2 (0.672.5 Hz), related to ICP pulse waves. Statistically significant differences (p1.7010-3, Bonferronicorrected Wilcoxon signed-rank tests) in pairwise comparisons between phases of ITs were found using the mean and standard deviation of JD and SF. These differences were mainly found in B2, where a lower irregularity and variability, together with less prominent time-frequency fluctuations, were found in the hypertension phase of ITs. Our results suggest that wavelet analysis could be useful for understanding CSF dynamics in NPH. This article is part of the theme issue 'Redundancy rules: the continuous wavelet transform comes of age'

Non-invasive Monitoring of Intracranial Pressure Using Transcranial Doppler Ultrasonography: Is It Possible?

Although intracranial pressure (ICP) is essential to guide management of patients suffering from acute brain diseases, this signal is often neglected outside the neurocritical care environment. This is mainly attributed to the intrinsic risks of the available invasive techniques, which have prevented ICP monitoring in many conditions affecting the intracranial homeostasis, from mild traumatic brain injury to liver encephalopathy. In such scenario, methods for non-invasive monitoring of ICP (nICP) could improve clinical management of these conditions. A review of the literature was performed on PUBMED using the search keywords 'Transcranial Doppler non-invasive intracranial pressure.' Transcranial Doppler (TCD) is a technique primarily aimed at assessing the cerebrovascular dynamics through the cerebral blood flow velocity (FV). Its applicability for nICP assessment emerged from observation that some TCD-derived parameters change during increase of ICP, such as the shape of FV pulse waveform or pulsatility index. Methods were grouped as: based on TCD pulsatility index; aimed at non-invasive estimation of cerebral perfusion pressure and model-based methods. Published studies present with different accuracies, with prediction abilities (AUCs) for detection of ICP ≥20 mmHg ranging from 0.62 to 0.92. This discrepancy could result from inconsistent assessment measures and application in different conditions, from traumatic brain injury to hydrocephalus and stroke. Most of the reports stress a potential advantage of TCD as it provides the possibility to monitor changes of ICP in time. Overall accuracy for TCD-based methods ranges around ±12 mmHg, with a great potential of tracing dynamical changes of ICP in time, particularly those of vasogenic nature.Cambridge Commonwealth, European & International Trust Scholarship (University of Cambridge) provided financial support in the form of Scholarship funding for DC. Woolf Fisher Trust provided financial support in the form of Scholarship funding for JD. Gates Cambridge Trust provided financial support in the form of Scholarship funding for XL. CNPQ provided financial support in the form of Scholarship funding for BCTC (Research Project 203792/2014-9). NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK provided financial support in the form of equipment funding for DC, BC and MC. The sponsors had no role in the design or conduct of this manuscript.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s12028-016-0258-

Human intracranial pulsatility during the cardiac cycle: a computational modelling framework

Background Today’s availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models’ validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model. Methods We develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest. Results Our model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle. Conclusions Our model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.publishedVersio

NON-INVASIVE MONITORING OF INTRACRANIAL PRESSURE USING TRANSCRANIAL DOPPLER ULTRASONOGRAPHY

Intracranial pressure (ICP) is an important monitoring modality in the clinical management of several neurological diseases carrying the risk of fatal intracranial hypertension. However, this parameter is not always considered due to its invasive assessment. In this scenario, a non-invasive estimation of ICP (nICP) may be essential, and indeed it has become a Holy Grail in Clinical Neurosciences: extensively searched, albeit never found. This thesis is devoted to the assessment, applications and development of transcranial Doppler (TCD)-based non-invasive methods for ICP and cerebral perfusion pressure (CPP) monitoring. The thesis is divided into three sections: I) The accuracy of existing TCD-based nICP estimators in various scenarios of varying ICP (traumatic brain injury, rise of ICP during plateau waves, and rise in ICP induced by infusion of cerebrospinal fluid during infusion test). The estimators of nICP consisted of a mathematical black box model, methods based on non-invasive CPP, and a method based on TCD pulsatility index. II) The feasibility of the best performing nICP estimator in clinical practice, including patients with closed TBI and brain midline shift, patients with acute liver failure during liver transplant surgery, and patients during non-neurosurgical surgery in the beach chair position. III) The description and assessment of a novel methodology for non-invasive assessment of cerebral perfusion pressure (nCPP) based on spectral arterial blood volume accounting. As main results, TCD-based non-invasive methods could replicate changes in direct ICP across time confidently, and could provide reasonable accuracy in comparison to the standard invasive techniques. Furthermore, in feasibility studies, nICP in association with other TCD physiological parameters provided a comprehensive interpretation of cerebral haemodynamics in conditions presenting impairment of cerebral blood flow circulation. The new method of nCPP estimation could identify changes in CPP across time reliably in conditions of decreasing and increasing CPP. These findings support the use of TCD-based nICP methods in a variety of clinical conditions requiring management of ICP and brain perfusion. More importantly, the low costs associated with nICP methods, since TCD is a widely available medical device, could contribute to its widespread use as a reliable alternative for ICP monitoring in everyday clinical practice.Cambridge Commonwealth European and Internation Trus

Caracterización de la señal de presión intracraneal y estudio de su relación con la respuesta a la implantación de un shunt en pacientes con hidrocefalia

El objetivo de este Trabajo Fin de Grado fue analizar las características espectrales de las señales PIC en pacientes con Hidrocefalia para estudiar las posibles diferencias entre aquellos pacientes que respondieron positivamente a la implantación de un shunt y los que no. Con este fin, se analizó la señal PIC de un total de 62 pacientes con Hidrocefalia sometidos a la implantación de un shunt, evaluándose en todos ellos la respuesta al tratamiento un año después de la cirugía. El análisis espectral de las señales se realizó en base a tres parámetros: frecuencia mediana, potencia relativa y entropía de Shannon. Estos parámetros se analizaron en dos bandas frecuenciales: B1 (0.15-0.3 Hz) y B2 (0.67-2.5 Hz). La primera, está relacionada con la componente respiratoria de la PIC, mientras que la segunda se asocia con la componente cardíaca. Asimismo, se distinguieron cuatro etapas en cada registro, relacionadas con las fases del test de infusión (basal, inicio de infusión, meseta y recuperación). El promedio de los tres parámetros fue obtenido para cada registro con el fin de identificar diferencias en las distribuciones de los pacientes que respondieron a la cirugía y aquellos que no. Además, se aplicaron métodos cualitativos y cuantitativos, basados en test estadísticos, para comparar ambas poblaciones en cada fase del test de infusión. No se apreciaron diferencias significativas entre los dos grupos de pacientes para los parámetros estudiados. Por ello, es necesario continuar la investigación en el futuro empleando nuevos parámetros espectrales y no lineales para tratar de determinar si alguno de ellos permite predecir satisfactoriamente la respuesta de un paciente a la implantación de un shunt.Hydrocephalus is a disease characterised by a significative accumulation of cerebrospinal fluid (CSF) and an increase of the intracranial pressure (ICP). It can appear at any age as a consequence of serious head injuries or as a result of other diseases. However, it can also appear without an evident cause (Idiopathic Hydrocephalus). The implantation of a shunt, which can reduce the pressure draining the excess of CSF in the brain, is the commonly accepted treatment. However, not all the patients have a positive response. Hydrodynamic tests, like infusion test, are used to evaluate each case. In infusion tests, ICP is deliberately increased and monitored for the purpose of evaluating the hydrodynamic cerebral response. However, the infusion test does not correctly predict the response to shunting. It is necessary to use alternative methods to better understand the pathophysiological processes associated with hydrocephalus. The main objective of this Final Degree Project was to analyse the spectral characteristics of ICP signals in patients with hydrocephalus in order to evaluate the differences between patients with a positive response to shunting and those with a negative. Sixty-two ICP signals of patients with hydrocephalus were studied for this purpose. The response to shunting was evaluated one year after surgery in all patients. The spectral analysis performed in this study was based on three parameters: median frequency, relative power and Shannon entropy. These parameters were studied in two frequency bands: 1(0.15-0.3 Hz), related to respiratory blood pressure oscillations and 2 (0.67-2.5 Hz) related to ICP pulse waves. Additionally, four artefact-free phases were analysed in each ICP recording, related to the different stages of infusion tests (basal, infusion, plateau and recovery). For each recording, the three parameters were averaged in order to study the differences in the distributions of those patients who responded positively to shunting and those who did not. Likewise, both groups were compared in each phase of the infusion test using qualitative and quantitative methods, as well as statistical tests. No statistically significant differences were found between both groups using these parameters. Further studies are needed in order to determine whether other spectral and non-lineal parameters can be useful to predict the response to shunting.Grado en Ingeniería de Tecnologías Específicas de Telecomunicació

Physiological and pharmacological modelling in neurological intensive care and anaesthesia

Mathematical models of physiological processes can be used in critical care and anaesthesia to improve the understanding of disease processes and to guide treatment. This thesis provides a detailed description of two studies that are related through their shared aim of modelling different aspects of brain physiology. The Relationship Between Transcranial Bioimpedance and Invasive Intracranial Pressure Measurement in Traumatic Brain Injury Patients (BioTBI) Study describes an attempt to model intracranial pressure (ICP) in patients admitted with severe traumatic brain injury (TBI). It is introduced with a detailed discussion of the monitoring and modelling of ICP in patients with TBI alongside the rationale for considering transcranial bioimpedance (TCB) as a non-invasive approach to estimating ICP. The BioTBI Study confirmed a significant relationship between TCB and invasively measured ICP in ten patients admitted to the neurological intensive care unit (NICU) with severe TBI. Even when using an adjusted linear modelling technique to account for patient covariates, the magnitude of the relationship was small (r-squared = 0.32) and on the basis of the study, TCB is not seen as a realistic technique to monitor ICP in TBI. Target controlled infusion (TCI) of anaesthetic drugs exploit known pharmacokinetic pharmacodynamic (PKPD) models to achieve set concentrations in the plasma or an effect site. Following a discussion of PKPD model development for the anaesthetic drug propofol, the Validation Study of the Covariates Model (VaSCoM) describes a joint PKPD study of the Covariates Model. Pharmacokinetic validation of plasma concentrations predicted by the model in forty patients undergoing general anaesthesia confirmed a favourable overall bias (3%) and inaccuracy (25%) compared to established PKPD models. The first description of the pharmacodynamic behaviour of the Covariates Model is provided with an estimated rate constant for elimination from the effect site compartment (ke0) of 0.21 to 0.27 min-1