Insinuating electronics in the brain

AbstractThere is an expanding interface between electronic engineering and neurosurgery. Rapid advances in microelectronics and materials science, driven largely by consumer demand, are inspiring and accelerating development of a new generation of diagnostic, therapeutic, and prosthetic devices for implantation in the nervous system. This paper reviews some of the basic science underpinning their development and outlines some opportunities and challenges for their use in neurosurgery

A Soft Robotic Actuator System for in vivo Modeling of Normal Pressure Hydrocephalus

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: In vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus

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

An Implantable Low Pressure, Low Drift, Dual BioPressure Sensor and In-Vivo Calibration Methods Thereof

The human body’s intracranial pressure (ICP) is a critical component in sustaining healthy blood flow to the brain while allowing adequate volume for brain tissue within the rigid structures of the cranium. Disruptions in the body’s autoregulation of intracranial pressure are often caused by hemorrhage, tumors, edema, or excess cerebral spinal fluid resulting in treatments that are estimated to globally cost up to approximately five billion dollars annually. A critical element in the contemporary management of acute head injury, intracranial hemorrhage, stroke, or other conditions resulting in intracranial hypertension, is the real-time monitoring of ICP. Currently, such mainstream clinical monitoring can only take place short-term within an acute care hospital. The monitoring is prone to measurement drift and is comprised of externally tethered pressure sensors that are temporarily implanted into the brain, thus carrying a significant risk of infection. To date, reliable, low drift, completely internalized, long-term ICP monitoring devices remain elusive. The successful development of such a device would not only be safer and more reliable in the short-term but would expand the use of ICP monitoring for the management of chronic intracranial hypertension and enable further clinical research into these disorders. The research herein reviews the current challenges of existing ICP monitoring systems, develops a new novel sensing technology, and evaluates the same for potentially facilitating long-term implantable ICP sensing. Based upon the findings of this research, this dissertation proposes and evaluates a dual matched-die piezo-resistive strain sensing device, with a novel in-vivo calibration system and method thereof, for application to long-term implantable ICP sensing

Volume 33, issue 1

The mission of CJS is to contribute to the effective continuing medical education of Canadian surgical specialists, using innovative techniques when feasible, and to provide surgeons with an effective vehicle for the dissemination of observations in the areas of clinical and basic science research. Visit the journal website at http://canjsurg.ca/ for more.https://ir.lib.uwo.ca/cjs/1236/thumbnail.jp

Implantable microdevice for the treatment of hydrocephalus

We present a novel microdevice for the treatment of hydrocephalus. Hydrocephalus is a pathological condition in which excessive cerebrospinal fluid (CSF) is accumulated within the subarachnoid space of the brain due to deficient arachnoid granulations, resulting in the brain damage or death. Current treatment for hydrocephalus is to surgically implant a shunt device to drain the excessive fluid from the ventricles to peritoneal cavity or other parts of the body. This method has over 50% failure rate due to occlusions and mechanical failures of shunt components. The proposed microfabricated device can mimic the function of normalarachnoid granulations and thus can replace the deficient arachnoid granulations. The microfabricated arachnoid granulations (MAG) consist of arrays of microvalves and microneedles.The microvalves are made of a PDMS/Parylene composite layer and have a 3-D dome petal shape. Such geometry enables the microvalve to rectify fluid flow in the forward and backward direction due to pressure differentials like normal arachnoid granulation. Microvalve design was optimized using 3-D numerical simulation. The microvalves were fabricated using three main microfabrication techniques: diffuser lithography for dome-shaped SU-8 mold fabrication, thin polymer film deposition and reflow for PDMS/Parylene membrane formation, and excimer laser machining for valve opening. The pressure drop vs. flow rate characteristics of the fabricated microvalve was investigated through in-vitro flow tests using a bench-top CSF simulator. The results showed that a 10x10 microvalve array with combined opening shape is optimal for our application.The microneedle array is to surgically pierce the dura mater membrane after being assembled with the microvalve. The microneedles were fabricated using three main techniques: diffraction photolithography for tapered SU-8 needle fabrication, RIE etching for needle sharpening, and excimer laser machining for through-hole creation. Puncture tests were conducted using pig’s dura mater and the microneedles coated with a Ti layer showed promising results (16 out of 100 needles pierced dura and the needles were not deformed). Blood adhesion tests were also carried out using human blood simulating the CSF dynamics and no significant platelet adhesion was observed at the microneedles. The MAG presented in this dissertation demonstrates a great potential for the treatment of hydrocephalus.Ph.D., Mechanical Engineering and Mechanics -- Drexel University, 201

Micro implantable pressure sensors for lifetime monitoring of intracranial pressure : this dissertation is submitted for the degree of Doctor of Philosophy, School of Engineering and Advanced Technology, Massey University

Permission for the re-use of Figures was obtained from Oxford University Press and BMJ Publishing Group Ltd.The elevation of intracranial pressure (ICP) associated with traumatic brain injury (TBI), hydrocephalus and other neurological conditions is a serious concern. If left untreated, increased pressure in the brain will reduce cerebral blood flow (CBF) and can lead to brain damage or early death. Currently, ICP is monitored through invasive catheters inserted into the brain along with a shunt. However, insertion of catheters or shunts is an invasive procedure that introduces vulnerability to infection. In principle, the risk of infection would be overcome by a fully implantable pressure monitoring system. This would be particularly valuable for hydrocephalus patients if lifetime monitoring was available. An implantable pressure monitoring system relies on a thin flexible membrane as part of the pressure sensor. The thin film membrane displaces under load and correspondingly induces a change in a relevant electrical quantity (resistance, or capacitance). Micro-electro-mechanical system (MEMS) is the technology that helps in creating micro/nano-mechanical structures integrated with signal conditioning electronics. These micro structures can be inserted into the brain, where the thin film is exposed to a corrosive fluid (saline/blood) at a temperature of approximately 37 ◦C. The miniaturization in MEMS permits examination, sensing and monitoring from inside the patient for longer durations. However, the accuracy, particularly in terms of sensor drift over long durations, is a key concern. In general, the issue of drift is attributed to the aging and mechanical fatigue of thin film structures, particularly the thin flexible membrane. Therefore, it is essential to analyze the thin film deflection and fatigue behaviour of MEMS pressure sensors for achieving long-term reliability and accuracy. Thus, the high-level goal of this research is to identify a viable approach to producing a flexible membrane suitable for deployment as a lifetime implantable pressure measuring system. In this context, finite-element modelling (FEM) and finite-element analysis (FEA) of thin film deflection and fatigue behaviour have been conducted. The FEM was implemented in COMSOL Multiphysics with geometries resembling a capacitive type pressure sensor with titanium (Ti) thin film membrane deposited onto the silicon substrate. The mechanical behavior of thin film structures including stresses, strains, elastic strain energy density, and thin film displacements of several thicknesses (50 μm, 25 μm, 4 μm, 1 μm, 500 nm, 200 nm) have been studied. In addition, fatigue physics module has been added to the FEM to analyze the fatigue life of thin film structures. The FEA results in the form of fatigue usage factors have been plotted. Finally, to analyze the effect of fluid pressure transmission of the thin film membrane inside the closed skull, fluid-structure interaction has been modelled. The model represents a 2D fluid medium with the thin film membrane. The velocity magnitude, displacement, shear rate (1/s) and kinetic energy density (J/m3) of 4 μm and 25 μm thick Ti films has been plotted. From this analysis, 4 μm thin film membrane showed good tradeoff for thickness, pressure transmission, and mechanical behaviour. To validate the FEM, a custom designed acoustic-based thin film deflection and fatigue life experiments have been set up. The experimental design comprised of: (1) A voice coil-based multimedia speaker and subwoofer system to assist in displacing the thin film membranes, (2) A laser displacement sensor to capture the displacements, (3) A spectrum analyzer palette for generating random vibrations, (4) Dataloggers to record the input vibrations and thin film displacements, and (5) Scanning electron microscopy (SEM) to visualize the surface topography of thin film structures. Thin film titanium (Ti) foils of 4 μm and 25 μm thick were obtained from William Gregor Ltd, Ti-shop, London. The thin-film specimens were clamped to 3mm acrylic substrates and bonded to the subwoofer system. The Gaussian random vibrations generated from the spectrum analyzer loaded the voice coil of the multi-media speaker system, which assists in displacing the thin films. The SEM surface observations are divided into two regions: (1) Pre-cycle observation, where the thin film surfaces are observed before the application of any load, and (2) Post-cycle observation, where the thin films surfaces are observed after application of cyclic loadings. Based on the understanding of the FEM and experimental studies, a conceptual framework of MEMS pressure sensor has been developed. In this part of the work, initially, underlying concepts of complementary-metal-oxide silicon (CMOS) circuit simulation, MEMS modelling, and CMOS layout design have been discussed. Next the MEMS fabrication process involving deposition (sputtering), etching, and final packaging have been discussed. Finally, an optimized design process of the membrane-based sealed cavity MEMS pressure sensors has been outlined

Tetralogy of Fallot in Finland

Abstract Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. Postoperative patients with TOF are mostly compromised by chronic pulmonary regurgitation and chronic right ventricular volume load. These patients suffer from impaired exercise capacity and have an increased risk of sudden cardiac death (SCD) and heart failure. This thesis investigates the long-term outcome of surgically corrected TOF patients in a population-based setting. It also assesses the effects of long-lasting pulmonary regurgitation (PR) in the postoperative state in children and adolescents with TOF and healthy control subjects. During the period from 1962 to 2007 a total of 600 patients with TOF were surgically corrected in Finland before the age of 15 years. The follow-up time of these patients was 23±12.1 years. We observed that: i. 514 (85%) patients were alive and living in Finland; 82 (14%) had died. Primary repair of TOF was found to predict lower mortality and longer event-free survival when compared with two-stage repair. The need for a transannular patch (TAP) in TOF surgery carried a higher risk of re-operation without impact on late survival. In addition to the population-based follow-up study, we conducted a single‑centre cross-sectional study including 45 patients after repair of tetralogy of Fallot (rTOF) and 45 healthy age- and gender-matched paediatric and adolescent volunteers as controls (CO). Cardiac magnetic resonance (CMR) imaging was performed on all the study subjects. We made the following observations: ii. Late gadolinium enhancement (LGE), detected with CMR after gadolinium contrast agent, was also found outside the surgically affected areas in the right ventricle (RV) of TOF patients. Severity of PR correlated with the degree of LGE. LGE is recognized as a marker of fibrosis, scars, or otherwise abnormal myocardium. iii. In children and adolescents with TOF, severe pulmonary regurgitation importantly affects volume flow through the left atrium. Reduction in left ventricular (LV) preload volume may be an additional factor contributing to LV dysfunction. iv. RV longitudinal strain is increased in paediatric TOF patients with severe pulmonary regurgitation. In comparison with healthy volunteers, all TOF patients demonstrated enhanced and delayed RV circumferential strain that was accentuated in the apical region. In conclusion, the late results of TOF surgery are excellent. Patients operated on in the last two decades can expect to have a life expectancy comparable to their healthy peers. Early primary correction and avoidance of TAP if possible are predictors of superior late outcome. Chronic pulmonary regurgitation has deleterious effects on both right and LV filling and function. Novel methods such as LGE analysis, feature tracking (FT), and evaluation of LV preload may prove valuable when assessing the need for pulmonary valve replacement (PVR).Vaikean synnynnäisen sydänvian ennuste on parantunut merkittävästi Nuorimpien potilaiden ennuste lähestyy verrokkiväestöä, mutta sydänlihas ja sen toiminta ovat kuitenkin potilailla poikkeavia terveisiin verrattuna. Sydämen rakennevika on kaikkein yleisin yhteen elimeen kohdistuva rakennevika. Näiden sairauksien ennuste on parantunut huomattavasti viime vuosikymmenien aikana, ja aikuisiän on saavuttanut jo yli 7000 suomalaista sydänlasta. Hyvästä ennusteesta ovat poikkeuksena syanoottiset sydänviat, joilla tarkoitetaan ryhmää synnynnäisiä sydänvikoja, joissa sydämen oikean ja vasemman puolen välillä on oikovirtaus aiheuttaen verenkierron happivajausta ja sinisyyttä. Potilailla, joilla on oikeaa kammiota kuormittava sydänvika, ennuste on edelleenkin merkittävästi verrokkiväestöä huonompi, ja potilailla on normaaliväestöä suurempi riski kuolla joko sydämen vajaatoiminnan tai sydänperäisen äkkikuoleman vuoksi. Yleisyydeltään suurin ja merkittävin syanoottinen sydänvika on Fallot'n tetralogia. Tutkimuksessa käytettiin koko väestön kattavaa synnynnäisten sydänvikojen rekisteriä, jonka avulla kaikkien Suomessa leikattujen Fallot-potilaiden sairastuvuutta, kuolleisuutta sekä erilaisten kirurgisten menetelmien vaikutusta myöhäistätuloksiin voitiin selvittää. Otimme tutkimukseen mukaan kaikki Suomessa alle 15-vuotiaana korjausleikatut Fallot-potilaat, joita oli yhteensä 601. Rekisterin tietoja käyttämällä ja niitä väestörekisteriin ja potilasasiakirjoihin yhdistämällä selvitimme 99,8% kattavuudella potilaiden myöhäistuloksen sekä merkittävältä osalta myös käytetyt kirurgiset menetelmät sekä uusintaleikkausten määrän. Lisäksi tutkimme kliinisessä potilas-verrokkiasetelmassa Fallot-lapsia ja nuoria sekä heidän ikäisiään terveitä verrokkihenkilöitä. Tutkimukseemme osallistui yhteensä 45 potilasta ja 48 tervettä verrokkihenkilöä. Tavoitteena oli selvittää sydämen magneettikuvaksella Fallot-potilaiden sydämen toimintaa ja vajaatoiminnan kehittymislöydöksiä lapsuus- ja nuoruusiässä. Tutkimustemme mukaan Fallot-potilaiden ennuste on parantunut merkittävästi vuosikymmenten aikana. Leikkauskuolleisuutta ei nykyvuosituhannella enää käytännössä ole ollut ja 2000-luvulla syntyneiden Fallot-lasten ennuste näyttää lähestyvän verrokiväestön eliniänennustetta. TOF potilaille kannattaa, mikäli vain mahdollista, tehdä varhaislapsuudessa suora kirurginen korjaus ilman edeltävää oireita lievittävää leikkausta. Potilaiden hankalin myöhäisongelma on vaikea keuhkovaltimoläppävuoto, jonka totesimme vähentävän keuhkojen läpi kiertävän veren määrää ja vaikuttavan haitallisesti sydämen vasemman puolen toimintaan. Tämä on uusi havainto. Löysimme Fallot-potilaiden sydämestä arpeutumiseen viittaavia löydöksiä magneettikuvauksen myöhäistehostuma-tekniikalla ja totesimme löydösten liittyvän seuranta-ajan pituuteen ja keuhkovaltimoläpän vuodon määrään. Magneettikuvauksen strain-analyysilla osoitimme, että TOF-potilaiden sydänlihaksen liikkuvuus on poikkeavaa ja liikehäiriön vaikeusasteella on yhteys keuhkovaltimoläpän vuotoon. Fallot-kirurgian ja jatkohoidon tulokset Suomessa ovat kansainvälistä huippuluokkaa. Toivomme näiden löydösten tuovan lisäinformaatiota Fallot-potilaiden lääketieteelliseen seurantaan, joko suoraan käytettynä tai osana tulevaisuudessa mahdollisesti kehitettäviä ennustemalleja, jotka hyödyntävät ja analysoivat laaja-alaisesti potilaasta tutkittuja muuttujia. Kummassakin tapauksessa ne voisivat auttaa hoitavia lääkäreitä jatkohoitoon ja uusintaleikkauksiin liittyvässä päätöksenteossa