Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it.

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.

Dual-Modality Volume Measurement Integrated on a Ventricular Assist Device.

OBJECTIVE: Ventricular assist devices (VADs) are implanted in patients suffering from end-stage heart failure to sustain the blood circulation. Real-time volume measurement could be a valuable tool to monitor patients and enable physiological control strategies to provide individualized therapy. However, volume measurement using one sensor modality requires re-calibration in the critical time post VAD implantation. METHODS: To overcome this limitation, we have integrated ultrasound and impedance volume measurement techniques into a cannula of an apical VAD. We tested both modalities across a volume range from 140-420 mL using two differently sized and shaped biventricular silicon heart phantoms, which were subjected to physiological pressures in an in-vitro test bench. We compared results from standard calibrated measurements with calculations found by a quadratic optimization for the single modality and their combination (dual-modality) and validated the results using twofold cross-validation. RESULTS: The dual-modality approach resulted in most favorable limits of agreement (LOA) of -0.83 ± 1.54% compared to -13.88 ± 5.90% for ultrasound and -43.45 ± 10.28% for electric impedance, separately. CONCLUSION: The results of the dual-modality approach were as accurate as the standard calibrated measurement and valid over a large range of volumes (140-420 mL). In this in-vitro study, we show how a dual-modality ventricular volume measurement of ultrasound and electric impedance increases the robustness and renders calibration obsolete. SIGNIFICANCE: Ventricular volumes could be measured accurately in the critical period post VAD implantation despite ventricular remodeling.

Multi-channel bioimpedance spectroscopy based on orthogonal baseband shifting.

Objective. Multi-channel bioimpedance spectroscopy (BIS) systems typically sample each channel's impedance sequentially using multiplexers and a single analog-to-digital converter. These systems may lose their real-time capability with an increasing number of channels, especially for low excitation frequencies. We propose a new method, called orthogonal baseband shifting (OBS), for high-speed parallel BIS data acquisition at multiple excitation frequencies with low hardware and computational effort.Approach. Similar to orthogonal frequency-division multiplexing, used for digital data transmission, OBS systems use channel-specific orthogonal carrier frequencies to modulate the voltage response of the tissue. Given a suitable choice of carrier frequencies, the modulated signals of all channels sum up without loss of information and cross-talk. The fast Fourier transform (FFT) of the summed signal reveals a spectrum of non-overlapping, interleaved BIS data from which the corresponding BIS data of each channel can be calculated.Main results. In simulations, the system design requires a minimum signal-to-noise ratio of 30 dB to achieve amplitude errors below 1% and phase errors below 0.8°. The hardware realization, called 'AixBIS', has been evaluated for impedance measurements between 0.1 and 10 Ω with multi-frequency excitations between 45 and 180 kHz. The impedance values acquired had an averaged precision of 3.67 mΩ, which is only 0.65‰ in relation to the measured impedance. The phase had a mean precision of 0.46°. Moreover,in vitromeasurements achieved 140 full spectrum acquisitions per second. The impedance change measured in a silicone heart phantom showed a high correlation of 0.83 with the ventricles volume change (flow).Significance. The proposed method enables very fast impedance acquisition of all channels. A complete measurement is performed in the time of a single FFT acquisition, which is equal to the resolution bandwidth of the FFT. In addition, portable and low-power multi-channel BIS devices profit from highly reduced hardware effort. The outstanding performance of OBS measurements with the AixBIS system have the potential forin vivoBIS measurements in real-time.

Improved Estimation of Left Ventricular Volume from Electric Field Modeling.

Volume measurement is beneficial in left ventricular assist device (LVAD) therapy to quantify patient demand. In principle, an LVAD could provide a platform that allows bioimpedance measurements inside the ventricle without requiring additional implants. Conductance measured by the LVAD can then be used to estimate the ventricular radius, which can be applied to calculate ventricular volume. However, established methods that estimate radius from conductance require elaborate individual calibration or show low accuracy. This study presents two analytical calculation methods to estimate left ventricular radius from conductance using electric field theory. These methods build on the established method of Wei, now considering the dielectric properties of muscle and background tissue, the refraction of the electric field at the blood-muscle boundary, and the changes of the electric field caused by the measurements. The methods are validated in five glass containers of different radius. Additional bioimpedance measurements are performed in in-vitro models that replicate the left ventricle's shape and conductive properties. The proposed analytical calculation methods estimate the radii of the containers and the in-vitro models with higher accuracy and precision than Wei's method. The lead method performs excellently in glass cylinders over a wide range of radii (bias: 1.66%-2.48%, limits of agreement < 16.33%) without calibration to specific geometries.

In Silico and in Vitro Conductivity Models of the Left Heart Ventricle.

Ventricular Assist Devices (VADs) are used to treat patients with cardiogenic shock. As the heart is unable to supply the organs with sufficient oxygenated blood and nutrients, a VAD maintains the circulation to keep the patient alive. The observation of the patient's hemodynamics is crucial for an individual treatment; therefore, sensors to measure quantifiable hemodynmaic parameters are desirable. In addition to pressure measurement, the volume of the left ventricle and the progress of muscle recovery seem to be promising parameters. Ongoing research aims to estimate ventricular volume and changes in electrical properties of cardiac muscle tissue by applying bioimpedance measurement. In the case where ventricular insufficiency is treated by a catheter-based VAD, this very catheter could be used to conduct bioimpedance measurement inside the assisted heart. However, the simultaneous measurement of bioimpedance and VAD support has not yet been realized, although this would allow the determination of various loading conditions of the ventricle. For this purpose, it is necessary to develop models to validate and quantify bioimpedance measurement during VAD support. In this study, we present an in silico and an in vitro conductivity model of a left ventricle to study the application of bioimpedance measurement in the context of VAD therapy. The in vitro model is developed from casting two anatomical silicone phantoms: One phantom of pure silicone, and one phantom enriched with carbon, to obtain a conductive behavior close to the properties of heart muscle tissue. Additionally, a measurement device to record the impedance inside the ventricle is presented. Equivalent to the in vitro model, the in silico model was designed. This finite element model offers changes in material properties for myocardium and the blood cavity. The measurements in the in vitro models show a strong correlation with the results of the simulation of the in silico model. The measurements and the simulation demonstrate a decrease in impedance, when conductive muscle properties are applied and higher impedances correspond to smaller ventricle cross sections. The in silico and in vitro models are used to further investigate the application of bioimpedance measurement inside the left heart ventricle during VAD support. We are confident that the models presented will allow for future evaluation of hemodynamic monitoring during VAD therapy at an early stage of research and development.

Advances in Hemodynamic Analysis in Cardiovascular Diseases Investigation of Energetic Characteristics of Adult and Pediatric Sputnik Left Ventricular Assist Devices during Mock Circulation Support.

The need to simulate the operating conditions of the human body is a key factor in every study and engineering process of a bioengineering device developed for implantation. In the present paper, we describe in detail the interaction between the left ventricle (LV) and our Sputnik left ventricular assist devices (LVADs). This research aims to evaluate the influence of different rotary blood pumps (RBPs) on the LV depending on the degree of heart failure (HF), in order to investigate energetic characteristics of the LV-LVAD interaction and to estimate main parameters of left ventricular unloading. We investigate energetic characteristics of adult Sputnik 1 and Sputnik 2 LVADs connected to a hybrid adult mock circulation (HAMC) and also for the Sputnik pediatric rotary blood pump (PRBP) connected to a pediatric mock circulation (PMC). A major improvement of the LV unloading is observed during all simulations for each particular heart failure state when connected to the LVAD, with sequential pump speed increased within 5000-10000 rpm for adult LVADs and 6000-13000 rpm for PRBP with 200 rpm step. Additionally, it was found that depending on the degree of heart failure, LVADs influence the LV in different ways and a significant support level cannot be achieved without the aortic valve closure. Furthermore, this study expands the information on LV-LVAD interaction, which leads to the optimization of the RBP speed rate control in clinics for adult and pediatric patients suffering from heart failure. Finally, we show that the implementation of control algorithms using the modulation of the RBP speed in order to open the aortic valve and unload the LV more efficiently is necessary and will be content of further research.

A Novel Control Method for Rotary Blood Pumps as Left Ventricular Assist Device Utilizing Aortic Valve State Detection.

A novel control method for rotary blood pumps is proposed relying on two different objectives: regulation of pump flow in accordance with desired value and the maintenance of partial support with an open aortic valve by the variation of pump speed. The estimation of pump flow and detection of aortic valve state was performed with mathematical models describing the first- and second generation of Sputnik rotary blood pumps. The control method was validated using a cardiovascular system model. The state of the aortic valve was detected with a mean accuracy of 91% for Sputnik 1 and 96.2% for Sputnik 2 when contractility, heart rate, and systemic vascular resistance was changed. In silico results for both pumps showed that the proposed control method can achieve the desired pump flow level and maintain the open state of the aortic valve by periodically switching between two objectives under contractility, heart rate, and systemic vascular resistance changes. The proposed method showed its potential for safe operation without adverse events and for the improvement of chances for myocardial recovery.

Real-Time ECG Simulation for Hybrid Mock Circulatory Loops.

Classically, mock circulatory loops only simulate mechanical properties of the circulation. To connect the hydraulic world with electrophysiology, we present a real-time electrical activity model of the heart and show how to integrate this model into a real-time mock loop simulation. The model incorporates a predefined conduction pathway and a simplified volume conductor to solve the bidomain equations and the forward problem of electrocardiography, resulting in a physiological simulation of the electrocardiogram (ECG) at arbitrary electrode positions. A complete physiological simulation of the heart's excitation would be too CPU intensive. Thus, in our model, complexity was reduced to allow real-time simulation of ECG-triggered medical systems in vitro; this decreases time and cost in the development process. Conversely, the presented model can still be adapted to various pathologies by locally changing the properties of the heart's conduction pathway. To simulate the ECG, the heart is divided into suitable areas, which are innervated by the hierarchically structured conduction system. To distinguish different cardiac regions, a segmentation of the heart was performed. In these regions, Prim's algorithm was applied to identify the directed minimal spanning trees for conduction orientation. Each node of the tree was assigned to a cardiac action potential generated by its hybrid automaton to represent the heart's conduction system by the spatial distribution of action potentials. To generate the ECG output, the bidomain equations were implemented and a simple model of the volume conductor of the body was used to solve the forward problem of electrocardiography. As a result, the model simulates potentials at arbitrary electrode positions in real-time. To verify the developed real-time ECG model, measurements were made within a hybrid mock circulatory loop, including a simple ECG-triggered ventricular assist device control. The model's potential value is to simulate physiological and pathological behavior for hardware-in-the-loop testing of medical devices in an ECG-triggered scenario.