Intracranial pressure estimation using nonlinear Kalman filtering

The intracranial hypertension is the medical name for high intracranial pressure, a condition that can be dangerous for the patient's health. This increase of intracranial pressure (ICP) may be caused by a congenital or acquired pathology (i.e. the hydrocephalus) as well as by the increasing volume of a cranial mass lesion, among others.\\\\ Considering that some of these pathologies are chronic, it is necessary to develop automatic drainage systems, so the human help is not needed (or at least reduced) in an emergency situation.\\\\ This thesis will deal with the design, implementation and improvement of an algorithm that predicts the intracranial pressure. It could be useful, for example, to able a device drain the cerebrospinal fluid (CSF) automatically when the pressure suddenly increases, common problem in Hydrocephalus patients. The cardiovascular model (R. Mondal et al.) will be used in order to emulate a patient and obtain an intracranial pressure estimation from aortic pressure measurements. Both signals will be processed with a Kalman filter variant (Unscented Kalman Filter), due to the cardiovascular model's non linearities, to obtain a prediction of the ICP.La hipertensión intracraneal (HTIC) es la condición en la que la presión intracraneal crece de manera que puede ser perjudicial para la salud del paciente. Este aumento de PIC (presión intracraneal) puede ser bien dado por una patología congénita o adquirida (como por ejemplo la hidrocefalia) como por una masa creciente fruto de una lesión craneal.\\\\ Teniendo en cuenta que algunas de estas patologías pueden ser crónicas, es necesario diseñar sistemas de drenaje automático de forma que no sea necesaria la intervención humana en caso de emergencia.\\\\ Este trabajo se centrará en diseñar e implementar un algoritmo de predicción de la presión intracraneal. Podría ser útil, por ejemplo, para hacer posible el drenaje de líquido cefalorraquídeo cuando se de un aumento espontáneo de presión, problema habitual en pacientes con Hidrocefalia. Se usará el modelo cardiovascular (R. Mondal et al.) que servirá para emular en modelo, y obtener una estimación de la PIC a partir de medidas de la presión aórtica. Ambas señales serán tratadas con una variante del filtro de Kalman (Unscented Kalman Filter), dada la no linealidad del modelo cardiovascular, para obtener una predicción de la presión intracraneal.La hipertensió intracranial (HTIC) és la condició en què la pressió intracranial creix de manera que pot ser perjudicial per a la salut del pacient. Aquest augment de PIC (pressió intracranial) pot ser tant donat per una patologia congènita o adquirida (per exemple, la hidrocefàlia) com per una massa creixent fruit d'una lesió cranial.\\\\ Tenint en compte que algunes d'aquestes patologies poden ser cròniques, és necessari dissenyar sistemes de drenatge automàtic de manera que no sigui necessària la intervenció humana en cas d'emergència. \\\\ Aquest treball es centrarà a dissenyar i implementar un algoritme de predicció de la pressió intracranial. Podria ser útil, per exemple, per fer possible el drenatge de líquid cefaloraquidi quan es doni un augment sobtat de pressió, problema habitual en pacients amb Hidrocefàlia. S'usarà el model cardiovascular (R. Mondal et al.) que servirà per emular un pacient, i obtenir una estimació de la pressió intracranial a partir de mesures de la pressió aòrtica. Ambdós senyals seran tractats amb una variant del filtre de Kalman (Unscented Kalman Filter), donada la no linearitat del model cardiovascular, per obtenir una predicció de la pressió intracranial

HYDI-DSI revisited: Constrained non-parametric EAP imaging without q-space re-gridding

Producción CientíficaHybrid Diffusion Imaging (HYDI) was one of the first attempts to use multi-shell samplings of the q-space to infer diffusion properties beyond Diffusion Tensor Imaging (DTI) or High Angular Resolution Diffusion Imaging (HARDI). HYDI was intended as a flexible protocol embedding both DTI (for lower -values) and HARDI (for higher -values) processing, as well as Diffusion Spectrum Imaging (DSI) when the entire data set was exploited. In the latter case, the spherical sampling of the q-space is re-gridded by interpolation to a Cartesian lattice whose extent covers the range of acquired b-values, hence being acquisition-dependent. The Discrete Fourier Transform (DFT) is afterwards used to compute the corresponding Cartesian sampling of the Ensemble Average Propagator (EAP) in an entirely non-parametric way. From this lattice, diffusion markers such as the Return To Origin Probability (RTOP) or the Mean Squared Displacement (MSD) can be numerically estimated. We aim at re-formulating this scheme by means of a Fourier Transform encoding matrix that eliminates the need for q-space re-gridding at the same time it preserves the non-parametric nature of HYDI-DSI. The encoding matrix is adaptively designed at each voxel according to the underlying DTI approximation, so that an optimal sampling of the EAP can be pursued without being conditioned by the particular acquisition protocol. The estimation of the EAP is afterwards carried out as a regularized Quadratic Programming (QP) problem, which allows to impose positivity constraints that cannot be trivially embedded within the conventional HYDI-DSI. We demonstrate that the definition of the encoding matrix in the adaptive space allows to analytically (as opposed to numerically) compute several popular descriptors of diffusion with the unique source of error being the cropping of high frequency harmonics in the Fourier analysis of the attenuation signal. They include not only RTOP and MSD, but also Return to Axis/Plane Probabilities (RTAP/RTPP), which are defined in terms of specific spatial directions and are not available with the former HYDI-DSI. We report extensive experiments that suggest the benefits of our proposal in terms of accuracy, robustness and computational efficiency, especially when only standard, non-dedicated q-space samplings are available.Ministerio de Ciencia e Innovación (PID2021-124407NB-I00 and TED2021-130758B-I00)Ministry of Science and Higher Education (Poland) (PPN/BEK/ 2019/1/00421

Diffusion sampling schemes: A generalized methodology with nongeometric criteria

Producción CientíficaPurpose:The aim of this paper is to show that geometrical criteria for designingmultishellq-space sampling procedures do not necessarily translate into recon-struction matrices with high figures of merit commonly used in the compressedsensing theory. In addition, we show that a well-known method for visitingk-space in radial three-dimensional acquisitions, namely, the Spiral Phyllotaxis,is a competitive initialization for the optimization of our nonconvex objectivefunction.Theory and Methods:We propose the gradient design method WISH (WeIght-ing SHells) which uses an objective function that accounts for weighted dis-tances between gradients withinM-tuples of consecutive shells, withMrangingbetween 1 and the maximum number of shellsS. All theM-tuples share thesame weight�M. The objective function is optimized for a sample of theseweights, using Spiral Phyllotaxis as initialization. State-of-the-art General Elec-trostatic Energy Minimization (GEEM) and Spherical Codes (SC) were used forcomparison. For the three methods, reconstruction matrices of the attenuationsignal using MAP-MRI were tested using figures of merit borrowed from theCompressed Sensing theory (namely, Restricted Isometry Property —RIP— andCoherence); we also tested the gradient design using a geometric criterion basedon Voronoi cells.Results:For RIP and Coherence, WISH got better results in at least one com-bination of weights, whilst the criterion based on Voronoi cells showed anunrelated pattern.Conclusion:The versatility provided by WISH is supported by better results.Optimization in the weight parameter space is likely to provide additionalimprovements. For a practical design with an intermediate number of gradients,our results recommend to carry out the methodology here used to determine theappropriate gradient table.Agencia Estatal de Investigación,(under Grants RTI2018-094569-B-I00,PID2020-115339RB-I00 and TED2021-130090B-I00)ESAOTE, Ltd (Grant/Award Number: 18IQBM

Efficient estimation of propagator anisotropy and non‐Gaussianity in multishell diffusion MRI with micro‐structure adaptive convolution kernels and dual Fourier integral transforms

Producción CientíficaPurpose:We seek to reformulate the so-called Propagator Anisotropy (PA) andNon-Gaussianity (NG), originally conceived for the Mean Apparent Propagatordiffusion MRI (MAP-MRI), to the Micro-Structure adaptive convolution ker-nels and dual Fourier Integral Transforms (MiSFIT). These measures describerelevant normalized features of the Ensemble Average Propagator (EAP).Theory and Methods:First, the indices, which are defined as the EAP’sdissimilarity from an isotropic (PA) or a Gaussian (NG) one, are analyticallyreformulated within the MiSFIT framework. Then a comparison between theresulting maps is drawn by means of a visual analysis, a quantitative assess-ment via numerical simulations, a test-retest study across the MICRA dataset (6subjects scanned five times) and, finally, a computational time evaluation.Results:Findings illustrate the visual similarity between the indices computedwith either technique. Evaluation against synthetic ground truth data, however,demonstrates MiSFIT’s improved accuracy. In addition, the test–retest studyreveals MiSFIT’s higher degree of reliability in most of white matter regions.Finally, the computational time evaluation shows MiSFIT’s time reduction upto two orders of magnitude.Conclusions:Despite being a direct development on the MAP-MRI represen-tation, the PA and the NG can be reliably and efficiently computed withinMiSFIT’s framework. This, together with the previous findings in the originalMiSFIT’s article, could mean the difference that definitely qualifies diffusionMRI to be incorporated into regular clinical settings.Ministerio de Educación, Junta de Castilla y León y Fondo Social Europeo, (Grant/Award Number: OrdenEDU/1100/2017 12/12)Ministerio de Ciencia e Innovación, Grant/AwardNumbers: (RTI2018-094569-B-I00),(PID2021-124407NB-I00)Ministry of Science and Higher Education of Poland,(Grant/Award Number:692/STYP/13/2018)Narodowa Agencja Wymiany Akademickiej, (Grant/AwardNumber: PPN/BEK/2019/1/00421

Anisotropy measure from three diffusion-encoding gradient directions

Producción CientíficaWe propose a method that can provide information about the anisotropy and orientation of diffusion in the brain from only 3 orthogonal gradient directions without imposing additional assumptions. The method is based on the Diffusion Anisotropy (DiA) that measures the distance from a diffusion signal to its isotropic equivalent. The original formulation based on a Spherical Harmonics basis allows to go down to only 3 orthogonal directions in order to estimate the measure. In addition, an alternative simplification and a color-coding representation are also proposed. Acquisitions from a publicly available database are used to test the viability of the proposal. The DiA succeeded in providing anisotropy information from the white matter using only 3 diffusion-encoding directions. The price to pay for such reduced acquisition is an increment in the variability of the data and a subestimation of the metric on those tracts not aligned with the acquired directions. Nevertheless, the calculation of anisotropy information from DMRI is feasible using fewer than 6 gradient directions by using DiA. The method is totally compatible with existing acquisition protocols, and it may provide complementary information about orientation in fast diffusion acquisitions.Ministerio de Ciencia e Innovación (grant RTI2018-094569-B-I00)Wellcome Trust Investigator Award (award 096646/Z/11/Z)Wellcome Trust Strategic Award (award 104943/Z/14/Z

RGD mutation of the heparin binding II fragment of fibronectin for guiding mesenchymal stem cell behavior on titanium surfaces

Installing bioactivity on metallic biomaterials by mimicking the extracellular matrix (ECM) is crucial for stimulating specific cellular responses to ultimately promote tissue regeneration. Fibronectin is an ECM protein commonly used for biomaterial functionalization. The use of fibronectin recombinant fragments is an attractive alternate to the use of full-length fibronectin because of the relatively low cost and facility of purification. However, it is necessary to combine more than one fragment, for example, the cell attachment site and the heparin binding II (HBII), either mixed or in one molecule, to obtain complete activity. In the present study, we proposed to install adhesion capacity to the HBII fragment by an RGD gain-of-function DNA mutation, retaining its cell differentiation capacity and thereby producing a small and very active protein fragment. The novel molecule, covalently immobilized onto titanium surfaces, maintained the growth factor-binding capacity and stimulated cell spreading, osteoblastic cell differentiation, and mineralization of human mesenchymal stem cells compared to the HBII native protein. These results highlight the potential capacity of gain-of-function DNA mutations in the design of novel molecules for the improvement of osseointegration properties of metallic implant surfaces.Peer ReviewedPostprint (author's final draft

Spherical means-based free-water volume fraction from diffusion MRI increases non-linearly with age in the white matter of the healthy human brain

Producción CientíficaThe term free-water volume fraction (FWVF) refers to the signal fraction that could be found as the cerebrospinal fluid of the brain, which has been demonstrated as a sensitive measure that correlates with cognitive performance and various neuropathological processes. It can be quantified by properly fitting the isotropic component of the magnetic resonance (MR) signal in diffusion-sensitized sequences. Using healthy subjects (178F/109M) aged 25-94, this study examines in detail the evolution of the FWVF obtained with the spherical means technique from multi-shell acquisitions in the human brain white matter across the adult lifespan, which has been previously reported to exhibit a positive trend when estimated from single-shell data using the bi-tensor signal representation. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the spherical means-based multi-shell FWVF parameter with age, at the same time, a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW corrected diffusion tensor imaging (DTI) leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to the studies conducted over the standard (single-component) DTI. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the conceivable reason for the variations observed in FA and MD parameters across the lifespan with previous studies under the standard diffusion tensor imaging.Ministerio de Ciencia e Innovación (MCIN-AEI) y FEDER-UE (grant PID2021-124407NB-I00)Ministerio de Ciencia e Innovación (MCIN-AEI) - Unión Europea “NextGenerationEU/PRTR” (grant TED2021-130758B-I00)Ministry of Science and Higher Education (Poland) - Bekker programme (grant PPN/BEK/2019/1/00421)Norwegian ExtraFoundation for Health and Rehabilitation (2015/FO5146)European Union's Horizon 2020 research and Innovation program (ERC 802998

Intracranial pressure estimation using nonlinear Kalman filtering

The intracranial hypertension is the medical name for high intracranial pressure, a condition that can be dangerous for the patient's health. This increase of intracranial pressure (ICP) may be caused by a congenital or acquired pathology (i.e. the hydrocephalus) as well as by the increasing volume of a cranial mass lesion, among others.\\\\ Considering that some of these pathologies are chronic, it is necessary to develop automatic drainage systems, so the human help is not needed (or at least reduced) in an emergency situation.\\\\ This thesis will deal with the design, implementation and improvement of an algorithm that predicts the intracranial pressure. It could be useful, for example, to able a device drain the cerebrospinal fluid (CSF) automatically when the pressure suddenly increases, common problem in Hydrocephalus patients. The cardiovascular model (R. Mondal et al.) will be used in order to emulate a patient and obtain an intracranial pressure estimation from aortic pressure measurements. Both signals will be processed with a Kalman filter variant (Unscented Kalman Filter), due to the cardiovascular model's non linearities, to obtain a prediction of the ICP.La hipertensión intracraneal (HTIC) es la condición en la que la presión intracraneal crece de manera que puede ser perjudicial para la salud del paciente. Este aumento de PIC (presión intracraneal) puede ser bien dado por una patología congénita o adquirida (como por ejemplo la hidrocefalia) como por una masa creciente fruto de una lesión craneal.\\\\ Teniendo en cuenta que algunas de estas patologías pueden ser crónicas, es necesario diseñar sistemas de drenaje automático de forma que no sea necesaria la intervención humana en caso de emergencia.\\\\ Este trabajo se centrará en diseñar e implementar un algoritmo de predicción de la presión intracraneal. Podría ser útil, por ejemplo, para hacer posible el drenaje de líquido cefalorraquídeo cuando se de un aumento espontáneo de presión, problema habitual en pacientes con Hidrocefalia. Se usará el modelo cardiovascular (R. Mondal et al.) que servirá para emular en modelo, y obtener una estimación de la PIC a partir de medidas de la presión aórtica. Ambas señales serán tratadas con una variante del filtro de Kalman (Unscented Kalman Filter), dada la no linealidad del modelo cardiovascular, para obtener una predicción de la presión intracraneal.La hipertensió intracranial (HTIC) és la condició en què la pressió intracranial creix de manera que pot ser perjudicial per a la salut del pacient. Aquest augment de PIC (pressió intracranial) pot ser tant donat per una patologia congènita o adquirida (per exemple, la hidrocefàlia) com per una massa creixent fruit d'una lesió cranial.\\\\ Tenint en compte que algunes d'aquestes patologies poden ser cròniques, és necessari dissenyar sistemes de drenatge automàtic de manera que no sigui necessària la intervenció humana en cas d'emergència. \\\\ Aquest treball es centrarà a dissenyar i implementar un algoritme de predicció de la pressió intracranial. Podria ser útil, per exemple, per fer possible el drenatge de líquid cefaloraquidi quan es doni un augment sobtat de pressió, problema habitual en pacients amb Hidrocefàlia. S'usarà el model cardiovascular (R. Mondal et al.) que servirà per emular un pacient, i obtenir una estimació de la pressió intracranial a partir de mesures de la pressió aòrtica. Ambdós senyals seran tractats amb una variant del filtre de Kalman (Unscented Kalman Filter), donada la no linearitat del model cardiovascular, per obtenir una predicció de la pressió intracranial