Design and Evaluation of Enhanced Mock Circulatory Platform Simulating Cardiovascular Physiology for Medical Palpation Training

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Article Design and Evaluation of Enhanced Mock Circulatory Platform Simulating Cardiovascular Physiology for Medical Palpation Training

Jae-Hak Jeong 1 , Young-Min Kim 2, Bomi Lee 1 , Junki Hong 1 , Jaeuk Kim 2 , Sam-Yong Woo 3 , Tae-Heon Yang 4,* and Yong-Hwa Park 1,*

1 Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Korea; [email protected] (J.-H.J.); [email protected] (B.L.); [email protected] (J.H.) 2 Future Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea; [email protected] (Y.-M.K.); [email protected] (J.K.) 3 Center for Mechanical Metrology, Division of Physical Metrology, Korea Research Institute of Standards and Science, 267 Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea; [email protected] 4 School of Electronic and Electrical Engineering, College of Convergence Technology, Korea National University of Transportation, 50 Daehak-ro, Daesowon-myeon, Chungcheongbuk-do, Chungju-si 27469, Korea * Correspondence: [email protected] (T.-H.Y.); [email protected] (Y.-H.P.); Tel.: +82-43-841-5324 (T.-H.Y.); +82-42-350-3235 (Y.-H.P.) Received: 4 July 2020; Accepted: 3 August 2020; Published: 6 August 2020

Abstract: This study presents a design and evaluation of a mock circulatory platform, which can reproduce blood pressure and its waveforms to provide palpation experience based on the human cardiovascular physiology. To reproduce the human cardiovascular behavior, especially the blood pressure, the proposed platform includes three major modules: heart, artery and reservoir modules. The heart module reproduces source pressure exerted on the whole system with a controlled time-proﬁle. The artery module consists of a resistance valve to adjust the open area of the vessel and a compliance chamber adjusting the wall stiﬀness of the ascending aorta. The designed platform was cross validated by comparing the theory with a lumped model, i.e., the windkessel model, the measurements from the mock circulatory platform and the real human body data. As a result, the ventricular and aortic pressure waveforms measured from the designed platform were well matched with those of the actual human body. Parametric studies regarding peripheral resistance and aortic compliance were done for the detailed correlation analysis between human cardiovascular physiology and blood pressure. Since the proposed platform is based on the actual cardiovascular physiology, adjusting the structural parameters of the components can reproduce realistic blood pressure waveforms in a controllable manner. This platform is applicable to blood pressure measurement sensor calibration, palpation training, and haptic feedback.

Keywords: cardiovascular; blood pressure; waveform; physiology; circulatory platform; windkessel model; ﬂuid–electric analogy; palpation

1. Introduction Palpation is a physical examination technique that determines the size, shape, and location of an anatomical structure by touching a body part with ﬁngers. The accuracy of palpation is highly dependent on the skill of the clinician and requires advanced training. In particular, during open surgery, surgeons rely heavily on palpation using a tactile sensation to check the patient’s condition or the

Appl. Sci. 2020, 10, 5433; doi:10.3390/app10165433 www.mdpi.com/journal/applsci Appl. Sci. 2020, 10, 5433 2 of 17 anatomy of the patient’s muscles, bones, and blood vessels [1,2]. Haptic sensation plays an important role in allowing most surgeons to avoid damage to healthy tissue and unintentional perforation/rupture of blood vessels. For this reason, palpation is an important procedure done before an open surgical process for locating hidden blood vessels beneath tissue by detecting pulses and distinguishing arteries from veins [3]. This procedure requires advanced training experience either on a number of human bodies or using the haptic palpation simulator, which is more cost-effective as long as it gives accurate pulse signatures matched to the human bodies. To date, most haptic palpation simulators have focused on developing portable simulators that deliver artificially created haptic feelings in conjunction with virtual reality, rather than developing devices that reflect human physiology for technical difficulties and costs [4–6]. Reproduction of the blood pressure waveform is important for palpation training. To be used in medical practice or diagnosis, it is necessary to reproduce the blood pressure waveforms of femoral, radial, and abdominal arteries [7,8]. For palpation training, a study was performed to implement a blood pressure waveform according to the patient’s age through a cam profile and delivering it to a hand phantom with a pneumatic actuator [9]. However, a method transmitting an artificially generated haptic sense based on electric actuators or motor-based multi-degree-of-freedom force feedback devices is limited in training a real feeling to the clinician. In addition, these methods have limitations that cannot provide in-depth training associated with the blood pressure waveforms based on the physiological characteristics of the human body. To overcome these limitations, this study proposes a mock circulatory platform simulating cardiovascular physiology of the human body for advanced haptic palpation training of arteries. This mock circulatory simulator aims not only to reproduce blood pressure waveforms in blood vessels identically, but also to realize the physiology of blood circulation in the human body for further in-depth studies on the cardiovascular physiology. Previous studies on cardiovascular simulators have been intended mainly for endurance testing of an artificial heart, artificial valve, or stent [10,11]. Moreover, even though they were designed to reproduce pulsations and anatomical structures, they cannot reproduce blood pressure waveforms in a controllable manner. To improve this, cardiovascular simulators of some previous studies reproduce the blood pressure waveform by regulating the input waveform of the ventricular pump and the resistance valve of the vein [12–16]. Among these, it tried to reproduce the change in stiffness of the vascular wall by pressing the fluid with an air spring to control compliance, but did not actually change the compliance of the vascular wall [16]. However, there is no detailed study on adjusting the compliance of the blood vascular wall. Having considered the previous works, this study aims to develop a mock circulatory platform for reproducing blood pressure waveforms in a controllable manner by adjusting the structural parameters of key components. The contribution of this work is to design, develop and evaluate a simulator that mimics the following human physiological behavior: firstly, the blood pressure waveforms in the left ventricle and the ascending aorta are the same as those of the human body; secondly, it mimics the physiological characteristics of the pressure waveform that changes with peripheral resistance and compliance of ascending aorta. Hence, the mock circulatory platform is able to reproduce various blood pressure waveforms according to different conditions (e.g., gender, age, and BMI) by adjusting resistance and compliance. Through this simulator, the correlation between the pressure waveform and the change of each parameter is evaluated and verified to see whether a realistic physiology is reproduced in the proposed approach. This paper is organized as follows. Section2 describes the human blood pressure waveforms and the windkessel model, which is one of the simplest mathematical models of the cardiovascular system. Section3 is about the design and simulation of the mock circulatory platform. Each component of the platform is designed to reproduce the physiological behavior of the human body and the designed platform is validated through the lumped model simulation. Section4 describes the results of experimental validation and parametric study on the developed platform. Section5 concludes with a discussion and suggestions for future works. Appl. Sci. 2020, 10, x FOR PEER REVIEW 3 of 17

system. Section 3 is about the design and simulation of the mock circulatory platform. Each component of the platform is designed to reproduce the physiological behavior of the human body and the designed platform is validated through the lumped model simulation. Section 4 describes Appl.the Sci.results2020, 10of, 5433experimental validation and parametric study on the developed platform. Section3 of 17 5 concludes with a discussion and suggestions for future works.

2.2. Modeling Modeling of of Cardiovascular Cardiovascular System System TheThe blood blood pressure pressure waveform waveform represents represents the the current current condition condition of of the the cardiovascular cardiovascular system system and and itsits components. components. This This depends depends on on physiological physiological parameters parameters including including the the diameter, diameter, length, length, sti stiffness,ffness, andand vascular vascular wall wall thickness thickness ofof componentscomponents suchsuch asas thethe heartheart and aorta. Therefore, Therefore, it it is is possible possible to tomodel model the the physiological physiological behavior behavior of of the cardiovascular system system byby analyzing analyzing the the blood blood pressure pressure waveform.waveform. The The cardiovascular cardiovascular system system consists consists of of the the left left ventricle, ventricle, atrium, atrium, valves valves and and blood blood vessels. vessels. BloodBlood vessels vessels can can be be classified classified into into ascending ascending aorta, aorta, descending descending aorta, aorta, abdominal abdominal aorta, aorta, renal renal artery, artery, femoralfemoral artery, artery, etc. etc. The The ventricle ventricle acts acts as as a a pulsating pulsating pump, pump, and and each each of of the the other other components components has has didifferentfferent viscoelastic viscoelastic properties. properties. Thus, Thus, the the blood blood pressure pressure waveform waveform has has a a complex complex shape, shape, and and the the WiggersWiggers diagram diagram shows shows its its standard standard [17 [17].].

2.1.2.1. Wiggers Wiggers Diagram: Diagram: A A Standard Standard Human Human Blood Blood Pressure Pressure Waveform Waveform TheThe Wiggers Wiggers diagram, diagram, which which is ais standard a standard for for human human cardiovascular cardiovascular signals, signals is shown, is shown in Figure in Figure1a. The1a. bloodThe blood pressure pressure of the of leftthe left ventricle ventricle and and aorta, aorta, and and the the volume volume of of the the left left ventricle, ventricle are, are shown. shown. LeftLeft ventricular ventricular blood blood pressure pressure ranges ranges up up to to 120 120 mmHg, mmHg, with with a a systolic systolic period period of of about about one-third one-third of of oneone cycle. cycle. Aortic Aortic blood blood pressure pressure ranges ranges from from 70 70 to to 120 120 mmHg, mmHg, records records the the highest highest blood blood pressure pressure in in thethe systolic systolic phase, phase, and and decreases decreases to to the the lowest lowest blood blood pressure pressure after after drawing drawing the the dicrotic dicrotic notch, notch, which which isis the the transient transient increase increase in in blood blood pressure pressure caused caused by by the the closing closing of of aortic aortic valve, valve, in in the the diastolic diastolic phase. phase. FigureFigure1b 1b shows shows the the blood blood pressure–volume pressure–volume curve curve of of the the left left ventricle, ventricle, which which depicts depicts a similara similar shape shape inin most most mammals. mammals. The The goal goal of of this this paper paper is is to to reproduce reproduce these these pressure pressure waveforms, waveforms, with with an an emphasis emphasis onon the the aortic aortic waveform. waveform. However, However, the the cardiovascular cardiovascular system system is is very very complex. complex. To To describe describe the the physiologicalphysiological behavior behavior of of the the blood blood pressure pressure wave, wave, a a proper proper but but simpler simpler model model is is required. required. For For this, this, thethe windkessel windkessel model model allows allows lumped lumped modeling modeling of of these these complex complex cardiovascular cardiovascular components components into into simplesimple ﬂuid fluid dynamic dynamic elements elements and and its its electric electric analogy analogy [18 [18].].

(a) (b)

FigureFigure 1. Human 1. Human blood bloodpressure pressure waveform: waveform: (a) Wiggers (a diagram,) Wiggers redrawn diagram based, onredrawn https:// commons.based on wikimedia.orghttps://commons.wikimedia.org/wiki/File:Wiggers_Di/wiki/File:Wiggers_Diagram_2.svg;(b) ventricularagram_2.sv pressure–volumeg; (b) ventricular loop. pressure–volume loop. 2.2. Windkessel Model 2.2. Windkessel Model The concept of the windkessel effect is shown in Figure2a. The windkessel means air chamber in German,The and concept is an air-springof the windkessel type capacity effect mountedis shown inin theFigure middle 2a. The of the windkessel pipe to control means the air flow chamber rate. Thein German, combination and ofis an air-spring air-spring eff ecttype and capacity peripheral mounted resistance in the inmiddle the windkessel of the pipe can to control reproduce the theflow properties of the elastic artery wall. The fluid dynamics model of the cardiovascular system lumped with the windkessel effect is called the windkessel model, which can be converted into an equivalent electrical circuit through fluid–electric analogy [19]. The windkessel model is classified according to the types of components, the 2-element model considering only resistance (R) and capacitance (C), Appl. Sci. 2020, 10, x FOR PEER REVIEW 4 of 17 rate. The combination of air-spring effect and peripheral resistance in the windkessel can reproduce the properties of the elastic artery wall. The fluid dynamics model of the cardiovascular system lumpedAppl. Sci.with2020 the, 10 windkessel, 5433 effect is called the windkessel model, which can be converted into an4 of 17 equivalent electrical circuit through fluid–electric analogy [19]. The windkessel model is classified according to the types of components, the 2-element model considering only resistance (푅) and capacitancethe 3-element (퐶), the model 3-element considering model considering up to characteristic up to characteristic resistance of resistance the vessel of ( RtheC), vessel and the (푅퐶 4-element), and the model4-element considering model considering up to inertance up ofto blood inertance flowing of blood through flowing the vessel through (L). Thethe 4-elementvessel (퐿). windkesselThe 4- elementmodel windkessel shown in Figure model2b shown is known in toFigure be an e2bff ective is known simplified to be model an effective to describe simplified the characteristics model to of describethe cardiovascular the characteristics system of [18 the]. In cardiovascular this model, the system inductor [18]. and In characteristic this model, resistance the inductor are connected and characteristicin parallel; resistance the capacitor are andconnected peripheral in parallel; resistance the are capacitor also connected and peripheral in parallel, resistance where the are two also groups connectedare connected in paral inlel, series. where the two groups are connected in series.

(a) (b)

FigureFigure 2. Windkessel 2. Windkessel model: model: (a) schematic (a) schematic diagram diagram of the of windkessel the windkessel effect eﬀ, ect,redrawn redrawn based based on on https://commons.wikimedia.org/wiki/File:Windkessel_effect.svghttps://commons.wikimedia.org/wiki/File:Windkessel_eﬀect.svg; (b);( 4b-element) 4-element windkessel windkessel model model

throughthrough fluid ﬂuid–electric–electric analogy, analogy, 푉(푡):V input(t): inputvoltage, voltage, 퐼(푡): inputI(t): current, input current, 푅: peripheralR: peripheral resistance, resistance, 푅퐶: characteristicRC: characteristic resistance, resistance, 퐿: inertance,L: inertance, 퐶: compliance.C: compliance.

FluidFluid–electric–electric analogy analogy is summarized is summarized in Table in 1. Table Blood1. Bloodpressure pressure is converted is converted to voltage, to voltage,fluid resistanceﬂuid resistance to electrical to electrical resistance, resistance, blood inertia blood to inertia inductance, to inductance, and elastic and artery elastic wall artery compliance wall compliance to capacitance.to capacitance. Each electrical Each electrical element element can be can formulated be formulated by fluid by- ﬂuid-dynamicdynamic parameters parameters as follows as follows [20]. [20].

TableTable 1. Fluid 1. Fluid mechanics, mechanics, their their electrical electrical analogy analogy and andcorresponding corresponding cardiovascular cardiovascular parameter parameter..

FluidFluid Dynamics Dynamics Electric Electric Analogy Analogy Cardiovascular Cardiovascular Parameters Parameters Pressure P [Pa] Voltage V [V = J/C] Blood pressure [mmHg] h i PressureFlow rate 푷Q [Pam3]/ s VoltageCurrent 푽 [VI=[AJ/=CC] /s] Blood pressureBlood ﬂow [mmHg rate [mL] /s] h i Volume V m33 Charge q [C] Blood volume [mL] Flow rate 푸 [m /s] Current 푰 [A = C/s] Blood flow rate [mL/sh] i Viscosity µ [Pa s] Resistance R [Ω] Blood resistance R Pa s/m3 · · VolumeCompliance 푽 [1m[31]/ Pa] ChargeCapacitance 풒 [CC][ F = C/V] BloodVessel’s volume wall [mL compliance] hE i Inertance I kg/m4 Inductance L [H = V s/A] Blood inertia · Blood resistance 푹 8µ[Pal ∙ ViscosityPoiseuille’s 흁law [PaQ∙ =s] ∆P ResistanceOhm’s law푹 [ΩI =] ∆V R = R R s/m3] πr4

ퟏ Capacitance 푪 [F = Compliance [1/Pa] 8µl Vessel’s wall compliance 푬 C/RV]= , (1) πr4 4 Inductance 푳 [9Hρl= Inertance 푰 [kg/m ] L = Blood inertia (2) V ∙ s/A] 4πr2 ∆푃 3 2∆푉 8휇푙 Poiseuille’s law 푸 = Ohm’s2π lawr l 1푰 =σ 3πr3l 푅 = 푅 C = − 푅 = 휋푟4 (3) Et 2Et r 1 3ρ Et RC = √LC = (4) πr2 2 r Equations (1)–(4) show how to calculate electric parameters based on the ﬂuid–electric analogy of the blood vessel to construct the windkessel model. Peripheral resistance R is determined by the viscosity of blood µ and the diameter r and length l of the blood vessels. Inertance L is determined by the diameter and length of the blood vessels and the density of blood ρ. Compliance C is determined Appl. Sci. 2020, 10, x FOR PEER REVIEW 5 of 17

9𝜌𝑙 𝐿= (2) 4𝜋𝑟 Appl. Sci. 2020, 10, 5433 5 of 17 2𝜋𝑟𝑙1 𝜎 3𝜋𝑟𝑙 𝐶= = (3) 𝐸𝑡 2𝐸𝑡 by the diameter and length of the blood vessels and the thickness t and stiffness of the vascular walls E. Characteristic resistance RC is determined by inertance1 3𝜌 𝐸𝑡 and compliance of the blood vessels. It can 𝑅 = √𝐿𝐶 = (4) be calculated from the diameter and length of𝜋𝑟 the blood2 𝑟 vessels, the thickness and stiffness of the vascular walls, and density of blood. Equations (1)–(4) show how to calculate electric parameters based on the fluid–electric analogy 3.of Designthe blood and vessel Simulation to construct of Mock the wind Circulatorykessel model. Platform Peripheral resistance 𝑅 is determined by the viscosityThe windkessel of blood 𝜇 modeland the can diameter reproduce 𝑟 and the bloodlength pressure 𝑙of the waveform,blood vessels. but doesInertance not reflect 𝐿 is determined physiology suchby the as thediameter diameter and changelength andof the reflected blood wavevessels of and the cardiovascularthe density of system.blood 𝜌 Hence,. Compliance it does 𝐶 not is reproducedetermined the by individual the diameter characteristics and length of of the the cardiovascular blood vessels components.and the thickness In this 𝑡 study,and stiffness to overcome of the thevascular limitations walls of 𝐸 the. Characteristic windkessel model, resistance a mock 𝑅 circulatory is determined platform by inertance that reproduces and compliance each component of the ofblood the circulatoryvessels. It can system be calculated was designed from and the fabricated. diameter and length of the blood vessels, the thickness and stiffness of the vascular walls, and density of blood. 3.1. 4-Element Windkessel Model 3. Design and Simulation of Mock Circulatory Platform Figure3a shows the electric circuit of the 4-element windkessel model for simulation. The windkesselThe windkessel model wasmodel simulated can reproduce using Matlab the ™blood2019a pressure and Simulink waveform,™ software but fromdoes MathWorks not reflect (Natick,physiology MA, such USA). as The the inputdiameter voltage change is the and ventricular reflected pressure wave of from the thecardiovascular Wiggers diagram system. in FigureHence,1a. it Indoes this not paper, reproduce the parameters the individual used in characteristics the simulation of are the as cardiovascular follows. The peripheral components. resistance In thisR study,is 1.5 Ωto includingovercome viscositythe limitations and peripheral of the windkessel resistance model, of vein a andmock body, circulatory inertance platformL is 0.02 that H, reproduces compliance eachC is 0.8component F, and characteristic of the circulatory resistance systemRC iswas 0.13 designedΩ. These and values fabricated. approximate the entire body as a single blood vessel, and include the peripheral resistance of the vein and body. Figure3b shows the simulation result3.1. 4-Element of the 4-element Windkessel windkessel Model model. As in the Wiggers diagram, the aortic pressure in the systole increasesFigure with 3a the shows ventricular the electric pressure circuit and thenof the slowly 4-element decreases windkessel in the diastole. model These for simulation. blood pressure The waveformswindkessel and model parameter was simulated conditions using are usedMatlab as™ a control2019a and for parameterSimulink™ studies software through from simulations.MathWorks (Natick,In this MA, study, U.S.). the The change input in voltage pulse pressure,is the ventricular which is pressure the difference from the between Wiggers systolic diagram and in diastolic Figure blood1a. In pressures,this paper, is the examined parameters at the used aorta. in Forthe easesimulation of comparison are as follows. of pulse The pressure, peripheral calculated resistance aortic 𝑅 pressuresis 1.5 Ω wereincluding normalized viscosity to theand aortic peripheral pressure resistance in Figure3 ofb, andvein shifted and body, to have inertance zero as the 𝐿 minimumis 0.02 H, pressure.compliance Figure 𝐶 is3 c0.8 shows F, and normalized characteristic aortic resistance pressure 𝑅 according is 0.13 Ω to. These peripheral values resistance. approximate As the a result, entire asbody the peripheralas a single resistanceblood vessel, increases, and include the pulse the pressure,peripheral which resistance is the amplitudeof the vein of and the body. aortic Figure pressure 3b waveform,shows the simulation decreases. result Figure of3d the shows 4-element normalized windke aorticssel model. pressure As accordingin the Wiggers to the diagram, change ofthe aortic aortic compliance.pressure in Asthe a systole result, asincreases the compliance with the of ventri the vascularcular pressure wall decreases, and then the pulseslowly pressure, decreases which in the is thediastole. amplitude These of blood the aortic pressure pressure waveforms waveform, increases.

(a) (b)

Figure 3. Cont. Appl. Sci. 2020, 10, x FOR PEER REVIEW 6 of 17 Appl. Sci. 2020, 10, 5433 6 of 17 (a) (b)

FigureFigure 3. Simulation3. Simulation of theof 4-elementthe 4-element windkessel windkessel model: model: (a) implemented (a) implemented electric circuitelectric of circuit the 4-element of the 4- windkesselelement windkessel model; (b) simulated model; (b pressure) simulated waveforms pressure at the waveforms ventricle and at the aorta; ventricle (c) normalized and aorta; aortic (c) pressurenormalized according aortic to pressure various peripheralaccording to resistance; various peripheral (d) normalized resistance; aortic pressure(d) normalized according aortic to various pressure aorticaccording compliance. to various aortic compliance.

However,In this study, since the the change windkessel in pulse model pressure, lumps thewhich entire is the body, difference it is diffi betweencult to reflect systolic the and physiology diastolic ofblood each componentpressures, is of examined the cardiovascular at the aorta system.. For ease In of the comparison human body, of pulse the pressure pressure, wave calculated is partially aortic dividedpressures from were the normalized descending to aorta the into aortic the pressure kidney throughin Figure the 3b renal, and artery, shifted passes to have through zero as the the abdominalminimum artery, pressure. and branchesFigure 3cinto shows both normalized legs through aortic the femoralpressure artery according to form to aperipheral reflected wave resistance. [21]. ThisAs phenomenona result, as the is peripheral not considered resistance in the increases, windkessel the models. pulse pressure, Therefore, which in order is the to amplitude reproduce of the the physiologyaortic pressure of the waveform, cardiovascular decreases. system Figure more 3 accurately,d shows normalized it is necessary aortic to pressure design a according simulator to that the implementschange of aortic each cardiovascular compliance. As component a result, as simultaneously. the compliance of the vascular wall decreases, the pulse pressure, which is the amplitude of the aortic pressure waveform, increases. 3.2. Design of Mock Circulatory Platform TheHowever, mock circulatory since the platform windkessel of this model study lumps mimics the the entire cardiovascular body, it componentsis difficult to to reflectsimulate the thephysiology physiology of of each the humancomponent cardiovascular of the cardiovas system.cular The system. platform In isthe designed human asbody, a one the atrium pressure and wave one ventricleis partially structure, divided to study from thehow descending each component aorta ofinto arteries the kidney contributes through to pulse the renal wave artery, generation. passes Inthrough this study, the the abdominal effects of respiration artery, and were branches not considered, into both so legs the through right atrium the femoraland right artery ventricle to form were a integratedreflected intowave the [21 reservoir.]. This phenomenon The right atrium is not considered and the right in the ventricle windkessel have amodels. major roleTherefore, in supplying in order bloodto reproduce to the lungs the physiology for respiration, of the and cardiovascular changes in bloodsystem pressure more accurately, due to breathing it is necessary are as to small design as a severalsimulator mmHg that and implements do not contribute each cardiovascular to changes component in the blood simultaneou pressure waveformsly. [22]. It consists of components such as the ventricle, atrium, valves, arteries, and peripheral resistances. In terms of 3.2. Design of Mock Circulatory Platform mechanical components, it consists of a pump that acts as a heart, tubes that simulate aorta and arteries, and a reservoirThe mock that circulatory acts as a platform vein and of peripheral this study resistance. mimics the cardiovascular components to simulate theFigure physiology4a shows of the the human layout cardiovascular of the mock circulatorysystem. The platform, platform whichis designed consists as aof one 4 modules.atrium and Theone heart ventricle module structu has are, chamber to study acting how as left each atrium component and a piston of arteries acting contributesas left ventricle. to pulse There wave are valvesgeneration. between In eachthis study, component: the effects a pulmonary of respiration valve were between not considered, the reservoir so andthe right atrium, atrium and aand mitral right valveventricle between were the integrated atrium and into ventricle. the reservoir. The fluid The isright pressurized atrium and in thethe ventricleright vent andricle goes have through a major the role aorticin supplying valve to theblood aorta to the simulation lungs for module. respiration, The and pulmonary changes valve in blood and pressure mitral valve due areto breathing membrane are valves,as small and as the several aortic mmHg valve is and a check do not valve contribute designed to to changes streamline in the to suppressblood pressure turbulence. waveform The artery [22]. It moduleconsists consists of components of ascending, such descending, as the ventricle, and abdominal atrium, valves, aorta, arteries, and implements and peripheral a femoral resistances. artery that In splitsterms into of twomechanical tubes at components, the branch. The it consists reservoir of modulea pump isthat intended acts as toa heart, realize tubes venous that and simulate peripheral aorta resistance.and arteries, It consists and a reservoir of a resistance that acts valve as a mountedvein and atperipheral the ends resistance. of tubes, including a femoral artery, and a reservoir that stores fluid. The arm phantom module and the renal artery branching to the Figure 4a shows the layout of the mock circulatory platform, which consists of 4 modules. The kidney are also implemented for further detailed physiological studies. Figure4b shows the fabricated heart module has a chamber acting as left atrium and a piston acting as left ventricle. There are valves new mock circulatory platform. The aortic components, except the ascending aorta, are made of between each component: a pulmonary valve between the reservoir and atrium, and a mitral valve rigid acrylic to suppress compliance. This is to perform a more precise parametric study by allowing between the atrium and ventricle. The fluid is pressurized in the ventricle and goes through the aortic adjustment of compliance only in the ascending aorta to which the compliance chamber is applied. valve to the aorta simulation module. The pulmonary valve and mitral valve are membrane valves, Appl. Sci. 2020, 10, x FOR PEER REVIEW 7 of 17 and the aortic valve is a check valve designed to streamline to suppress turbulence. The artery module consists of ascending, descending, and abdominal aorta, and implements a femoral artery that splits into two tubes at the branch. The reservoir module is intended to realize venous and peripheral resistance. It consists of a resistance valve mounted at the ends of tubes, including a femoral artery, and a reservoir that stores fluid. The arm phantom module and the renal artery branching to the kidney are also implemented for further detailed physiological studies. Figure 4b shows the fabricated new mock circulatory platform. The aortic components, except the ascending aorta, are made of rigid acrylic to suppress compliance. This is to perform a more precise parametric studyAppl. Sci. by2020 allowing, 10, 5433 adjustment of compliance only in the ascending aorta to which the compliance7 of 17 chamber is applied.

(a)

(b)

FigureFigure 4. 4. DesignDesign of of mock mock circulatory circulatory platform: platform: (a (a) )drawing; drawing; (b (b) )fabricated fabricated platform. platform.

Pressure measurements are made at two points: ventricle and ascending aorta. This is to measure the input pressure waveform to which the ﬂuid is pressurized and the aortic pressure waveform transmitted through the aortic valve. Pressure waveforms at the ventricular pump and ascending aorta are measured with the PST164 pressure sensor from EFE (Ivry-la-Bataille, France) and sampled with 1 kHz sampling rate by the USB-6003 data acquisition device from NI (Austin, TX, USA). A linear motor was used as the ventricular pump, and it was controlled by the SPiiPlusCMnt motor controller from ACS motion control (Israel). The control cycle is 100 Hz, and acceleration up to 5 g is possible. Throughout this study, the ﬂuid inside the system was assumed as pure water, with density ρ = 1000 kg/m3 Appl. Sci. 2020, 10, x FOR PEER REVIEW 8 of 17

Pressure measurements are made at two points: ventricle and ascending aorta. This is to measure the input pressure waveform to which the fluid is pressurized and the aortic pressure waveform transmitted through the aortic valve. Pressure waveforms at the ventricular pump and ascending aorta are measured with the PST164 pressure sensor from EFE(Ivry-la-Bataille, France) and sampled with 1 kHz sampling rate by the USB-6003 data acquisition device from NI(Austin, Texas, U.S.). A linear motor was used as the ventricular pump, and it was controlled by the SPiiPlusCMnt motor controllerAppl. Sci. 2020from, 10 ACS, 5433 motion control(Israel). The control cycle is 100 Hz, and acceleration up to 5 g8 ofis 17 possible. Throughout this study, the fluid inside the system was assumed as pure water, with density 휌 = 1000 kg/m3 and viscosity 휇 = 1.0016 × 10−3 Pa ∙ s. A low-frequency filter was applied to the 3 measuredand viscosity pressureµ = waveform,1.0016 10 − sincePa s impulsive. A low-frequency noise is filter generated was applied when the to the aortic measured valve pressurecloses. × · However,waveform, the sincedicrotic impulsive notch was noise also is suppressed generated whenalong with the aortic valve valveclosing closes. noise. However, the dicrotic notch was also suppressed along with valve closing noise. 3.3. Adjustable Components of Mock Circulatory Platform 3.3. Adjustable Components of Mock Circulatory Platform The new mock circulatory platform of this study can change parameters for physiological study. As the bloodThe new pressure mock circulatorywaveform is platform reproduced of this in studythe windkessel can change model, parameters parameters for physiological such as stiffness study. andAs resistance the blood pressure of the components waveform is mustreproduced be adjustable in the windkessel in order model, to control parameters the waveform. such as sti Theffness pressurizingand resistance cylinder of the componentsapplied to the must reservoir be adjustable adjusts in the order minimum to control pressure the waveform. of the Theplatform. pressurizing The compliancecylinder applied of the platform to the reservoir is adjustable adjusts in the ascending minimum aorta. pressure It is ofadjusted the platform. through The a pressurizing compliance of cylinderthe platform in the compliance is adjustable chamber in ascending applied aorta. to the It ascending is adjusted aorta. through a pressurizing cylinder in the compliance chamber applied to the ascending aorta. FigureFigure 5a5 ashows shows the the reservoir reservoir with with a apressurizing pressurizing cylinder cylinder and and Figure Figure 5b5b shows shows the the co compliancempliance chamberchamber with with a pressurizing a pressurizing cylinder cylinder at atthe the ascending ascending aorta, aorta, which which are are included included in inthe the new new mock mock circulatorycirculatory platform platform of this of this study. study. To change To change the compliance, the compliance, the most the mosteffective effective way is way to change is to change the materialthe material of vascular of vascular wall wallwith withdifferent different complian compliances,ces, but butthis thisis very is very inconvenient inconvenient to be to berealized. realized. Hence,Hence, as asan an alternative, alternative, the the reservoir reservoir structure structure,, as asshown shown in inFigure Figure 5a5,a, has has been been used used to to realize realize the the changechange of ofcompliance compliance in inthe the existing existing cardiovascular cardiovascular simulators simulators [12 [12–15].–15 ].In Inthe the existing existing simulators, simulators, fluidfluid in inthe the reservoir reservoir is ispressurized pressurized by by the the air air spring spring on on the the top top of ofit to it totry try to tochange change the the compliance. compliance. However,However, the the amount amount of ofcompliance compliance change change was was not not enough enough to togenerate generate effective effective pulse pulse pressure pressure changeschanges to to be be detected detected in in the palpation training.training. Rather,Rather, it i changest changes the the minimum minimum pressure pressure of the of entirethe entiresystem system in a veryin a very sensitive sensitive way. way.

(a) (b)

FigureFigure 5. Adjustable 5. Adjustable components components of platform: of platform: (a) (raeservoir) reservoir with with pressurizing pressurizing cylinder; cylinder; (b) ( bcompliance) compliance chamberchamber with with pressurizing pressurizing cylinder. cylinder.

In this study, to magnify the pulse pressure, as shown in Figure5b, a vascular wall of ascending aorta made of ﬂexible silicone is added, which is pressurized by the air spring surrounding it to try to change the compliance. Therefore, the compliance of the vascular wall in the platform is actually adjusted. Using this new compliance chamber, experimental parametric study on change of compliance of aorta was done in Section4. Besides the compliance of the vascular wall, the peripheral resistance of the platform is controlled by ball valves mounted on the vein, and inertance can be controlled by changing the ﬂuid. Among all the adjustable components, the change of compliance of the vascular wall and the resistance are considered in this study. Appl. Sci. 2020, 10, x FOR PEER REVIEW 9 of 17

In this study, to magnify the pulse pressure, as shown in Figure 5b, a vascular wall of ascending aorta made of flexible silicone is added, which is pressurized by the air spring surrounding it to try to change the compliance. Therefore, the compliance of the vascular wall in the platform is actually adjusted. Using this new compliance chamber, experimental parametric study on change of compliance of aorta was done in Section 4. Besides the compliance of the vascular wall, the peripheral resistance of the platform is controlled by ball valves mounted on the vein, and inertance can be controlled by changing the fluid. Among all the adjustable components, the change of compliance of Appl. Sci. 2020, 10, 5433 9 of 17 the vascular wall and the resistance are considered in this study.

3.4.3.4. Simula Simulationtion Model Model of of Mock Mock Circulatory Circulatory Platform Platform FigureFigure 6 shows the simulation model of the mock circulatory platform obtained from the same fluidﬂuid–electric–electric analogy applied toto aa simplesimple modelmodel in in Figures Figures2 and2 and3, but3, but the the number number of components of components are areincreased. increased. In the In modelingthe modeling procedure, procedure, each componenteach component of the of mock the circulatorymock circulatory platform platform was lumped was lumpedinto a 4-element into a 4-element windkessel windkessel model [ 23model]. [23].

Figure 6. Simulation model of the mock circulatory platform. Figure 6. Simulation model of the mock circulatory platform.

TableTable 2 2lists lists the the parameters parameters of the of components the components of the mock of circulatory the mock platform circulatory and platfor correspondingm and correspondingelectric parameters. electric These parameters. are data reﬂecting These the are physiology data reflecting of actual the human physiology cardiovascular of actual components. human However, most of the aorta of the mock circulatory platform of this study are made of rigid acrylic, so the compliance is low compared to the human body. Appl. Sci. 2020, 10, 5433 10 of 17

Table 2. Parameters of cardiovascular components.

# Name Length l [mm] Diameter d [mm] Stiﬀness E [MPa] R [Ω] L [H] C [F] RC [Ω] Ascending 1 100 18.5 10 3.48 10 2 4.19 10 3 0.249 3.23 10 2 Aorta × − × − × − Descending 2 220 17.3 2500 0.100 1.05 10 2 1.79 10 3 4.34 10 3 Aorta × − × − × − Abdominal 3 88 10 2500 0.359 1.26 10 2 1.38 10 4 1.32 10 3 Aorta × − × − × − Femoral 4 200 6.4 2 7.30 0.105 0.154 0.127 Artery Pulmonary 2 3 5 107 6.4 2500 2.60 3.74 10− 1.28 10− Valve × - × 6 Mitral Valve 91.7 22.9 2500 1.36 10 2 2.50 10 3 2.08 10 3 × − × − × − 7 Aortic Valve 84 26.9 2500 6.55 10 3 1.66 10 3 2.07 10 3 × − × − × −

Table3 shows electrical parameters for some non-tubular components. There are non-tubular components of the mock circulatory platform, such as the reservoir, atrium, and ventricle. Electric parameter values of these components were tuned within the same order of magnitude as the vessel. Based on the above parameters, a parametric study was conducted on the simulation of the mock circulatory platform. The parametric study was performed by changing the values in 5 steps for peripheral resistance at the end of the femoral artery and compliance with ascending aorta.

Table 3. Parameters of non-tubular components.

Parameter Name R [Ω] L [H] C [F] RC [Ω] 1 Reservoir 1.00 10 4 0.01 0.1 0.0316 × − 2 Atrium 1.00 10 4 0.01 0.1 0.0316 × − 3 Ventricle 1.00 10 4 0.01 0.1 0.0316 × − 4 Leg Resistance Valve 1 1.00 - 5 Leg Resistance Valve 2 1.00

Figure7a shows the simulation result of the mock circulatory platform. The ventricular pressure in the Wiggers diagram was used as the input to the ventricular voltage source. The simulation shows that the systolic peak and diastolic slopes are reproduced almost identically to the Wiggers diagram within the 70–120 mmHg range. However, most of the aorta of the mock circulatory platform of this study are made of rigid acrylic, so the compliance (i.e., inverse of stiffness) is very low compared to the human body. Therefore, the dicrotic notch is suppressed and difficult to be observed. In this study, the change in pulse pressure, which is the difference between systolic and diastolic blood pressures, is examined at the aorta. For ease of comparison of pulse pressure, calculated aortic pressures were normalized to the aortic pressure in Figure7a, and shifted to have zero as the minimum pressure. Figure7b shows the normalized aortic pressure according to peripheral resistance. As a result, as the peripheral resistance increases, the pulse pressure, which is the amplitude of the aortic pressure waveform, decreases. Figure7c shows the normalized aortic pressure according to the change of aortic compliance. Compliance decreases inversely with increasing stiffness of the vascular wall. As a result, as the compliance of the vascular wall decreases (the stiffness of the blood vessel wall increases), the pulse pressure, which is the amplitude of the aortic pressure waveform, increases. This is the same result as the higher age; the stiffness of the vascular wall increases, the diastolic blood pressure rises, and the systolic blood pressure rises and the pulse pressure increases. Table4 shows the di fferences, advantages, and disadvantages of the platform of this study and the 4-element windkessel model through simulation. The mock circulatory platform of this study has the advantages of controlling the parameters of each artery component, measuring the pressure waveform, and reproducing accurate and detailed waveforms. However, the disadvantage is that dicrotic notches are difficult to observe due to low compliance. This can be improved by replacing other arterial components from rigid acrylics to flexible tubes. Appl. Sci. 2020, 10, x FOR PEER REVIEW 11 of 17

pressures were normalized to the aortic pressure in Figure 7a, and shifted to have zero as the minimum pressure. Figure 7b shows the normalized aortic pressure according to peripheral resistance. As a result, as the peripheral resistance increases, the pulse pressure, which is the amplitude of the aortic pressure waveform, decreases. Figure 7c shows the normalized aortic pressure according to the change of aortic compliance. Compliance decreases inversely with increasing stiffness of the vascular wall. As a result, as the compliance of the vascular wall decreases (the stiffness of the blood vessel wall increases), the pulse pressure, which is the amplitude of the aortic pressure waveform, increases. This is the same result as the higher age; the stiffness of the Appl.vascular Sci. 2020 wall, 10, 5433increases, the diastolic blood pressure rises, and the systolic blood pressure rises11 of and 17 the pulse pressure increases.

(a)

(b) (c)

FigureFigure 7. 7.Parametric Parametric study study of the of mock the circulatorymock circulatory platform platform simulation simulation model: (a) simulated model: (a ventricular) simulated andventricular aortic pressure and aortic waveforms; pressure (b) normalized waveforms; aortic (b) pressure normalized according aortic to pressure various peripheral according resistance; to various (cperipheral) normalized resistance; aortic pressure (c) normalized according aortic to various pressure aortic according compliance. to various aortic compliance.

Table 4. Comparison of the mock circulatory platform and the 4-elements windkessel model. Table 4 shows the differences, advantages, and disadvantages of the platform of this study and the 4-elementComparison windkessel Factor model through 4-Element simulation. Windkessel The mock Model circulatory Mock platform Circulatory of this Platform study has the Control advantages of individual of controlling component the parameters of each No artery component, measuring Yes the pressure waveform,Measurement and of individualreproducing component accurate and detailed waveforms. No However, the disadvantage Yes is that dicroticDelay notches after ventricleare difficult pressure to observe due to low compliance. No This can be improved Yes by replacing other arterialDicrotic components notch from rigid acrylics to flexible Yes tubes. No

4. ExperimentalTable 4. ValidationComparison and of the Parametric mock circulatory Study platform and the 4-elements windkessel model.

The mock circulatory system fabricated4-Element in this studyWindkessel was evaluated Mock through Circulatory experiments. Comparison Factor As in the simulation model, pure water (tertiary distilledModel water) was used asPlatform the internal ﬂuid. Peripheral resistance is controlled by changing the open area by turning the knob on the resistance valve, and aortic compliance is controlled by applying additional pressure using the compliance chamber. The experiment was performed at a normal heart rate of 80 BPM, the stroke of the ventricular pump was 10 mm, and the preload, the minimum ventricular volume, was performed at 20 mm. After initial driving, the aortic pressure was adjusted to 70–120 mmHg through the peripheral resistance valve.

4.1. Experimental Results and Validation The fabricated mock circulatory platform can reproduce ventricular pressure waveforms and aortic pressure waveforms very similar to the Wiggers diagram, like the simulation model. Figure8a shows Appl. Sci. 2020, 10, x FOR PEER REVIEW 12 of 17

Control of individual component No Yes

Measurement of individual No Yes component

Delay after ventricle pressure No Yes

Dicrotic notch Yes No

4. Experimental Validation and Parametric Study The mock circulatory system fabricated in this study was evaluated through experiments. As in the simulation model, pure water (tertiary distilled water) was used as the internal fluid. Peripheral resistance is controlled by changing the open area by turning the knob on the resistance valve, and aortic compliance is controlled by applying additional pressure using the compliance chamber. The experiment was performed at a normal heart rate of 80 BPM, the stroke of the ventricular pump was 10 mm, and the preload, the minimum ventricular volume, was performed at 20 mm. After initial driving, the aortic pressure was adjusted to 70–120 mmHg through the peripheral resistance valve.

4.1. Experimental Results and Validation

Appl. Sci.The2020 fabricated, 10, 5433 mock circulatory platform can reproduce ventricular pressure waveforms12 ofand 17 aortic pressure waveforms very similar to the Wiggers diagram, like the simulation model. Figure 8a shows the input volume waveform of the ventricular pump. In the early systolic period, it is the input volume waveform of the ventricular pump. In the early systolic period, it is compressed with compressed with a biased sine wave, and in the late diastolic period, it expands with constant a biased sine wave, and in the late diastolic period, it expands with constant velocity. Systolic is 30% of velocity. Systolic is 30% of the total cycle period. Figure 8b shows the pressure waveforms measured thefrom total the cycle fabricated period. mock Figure circulatory8b shows platform. the pressure It can waveforms be seen that measured this matches from well the fabricatedwith the Wiggers mock circulatory platform. It can be seen that this matches well with the Wiggers diagram, a human standard diagram, a human standard blood pressure waveform of Figure 1a. The angle of the resistance valve bloodknob pressureis 45 degrees, waveform and the of compliance Figure1a. The chamber angle is of in the the resistance state where valve no additional knob is 45 pressure degrees, is and applied. the compliance chamber is in the state where no additional pressure is applied. These blood pressure These blood pressure waveforms and parameter conditions are used as a control for parameter waveformsstudies through and parameter experiments. conditions Figure are 8 usedc shows as a controla ventricular for parameter pressure studies × 10— throughvolume experiments. loop of the Figure8c shows a ventricular pressure 10—volume loop of the fabricated mock circulatory platform. fabricated mock circulatory platform.× This is similar to the pressure × 10—volume loop calculated This is similar to the pressure 10—volume loop calculated from the Wiggers diagram of Figure1b. from the Wiggers diagram of× Figure 1b.

Appl. Sci. 2020, 10, x FOR PEER(a )REVIEW (b) 13 of 17

(c)

FigureFigure 8. 8.Baseline Baseline experiment experiment result: result: (a ()a volume) volume waveform; waveform; (b ()b pressure) pressure waveforms; waveforms; (c )(c ventricular) ventricular pressurepressure 10—volume× 10—volume loop loop of of mock mock circulatory circulatory platform. platform. × However,However, most most of of the the aorta aorta are are made made of of acrylic acrylic for for parameter parameter control control in in the the mock mock circulatory circulatory platformplatform of of this this study. study. Therefore, Therefore, the the dicrotic dicrotic notch notch is is very very small small in in the the aortic aortic pressure pressure waveform waveform becausebecause the the overall overall compliance compliance is is very very small small compared compared to to the the human human body. body. In In addition, addition, the the dicrotic dicrotic notchnotch is coveredis covered because because it is generatedit is generated at the at same the timesame as time the valve as the closing valve noise, closing and noise, is rarely and observed is rarely sinceobserved it is removed since it is together removed with together the valve with closing the val noiseve closing by a noise low pass by a ﬁlter. low passMoreover, filter. sinceMoreover the , ventricularsince the ventricular pump is made pump of rigidis made acrylic, of rigid unlike acrylic, the human unlike bodythe human with high body compliance, with high compliance, the stroke volumethe stroke required volume for required blood pressure for blood generation pressure is generation small, and is isovolumic small, and compressionisovolumic compression and relaxation and arerelaxation impossible. are impossible.

Figure 9a shows pressure waveform according to area ratio. In the case of ventricular pressure, systolic pressure increases as peripheral resistance increases, diastolic pressure decreases, and as a result, peak-to-peak amplitude increases. In the case of aortic pressure, systolic pressure increases as peripheral resistance increases, diastolic pressure increases more, and as a result, peak-to-peak amplitude decreases. Figure 9b shows the normalized aortic pressure waveform. To compare the pulse pressure, measured aortic pressures were normalized to the baseline aortic pressure in Figure 8b, and shifted to have zero as the minimum value. As the valve angle decreases, the area ratio decreases and the peripheral resistance increases. At the same time, it can be seen that the pulse pressure decreases. This is consistent with the change in pulse pressure according to the peripheral resistance predicted through the simulation model of Figure 7b. Therefore, the mock circulatory platform of this study can reproduce the blood pressure waveform according to the peripheral resistance. Appl. Sci. 2020, 10, 5433 13 of 17

4.2. Parametric Study on Peripheral Resistance Parametric studies of peripheral resistance were performed experimentally. The peripheral resistance is controlled through the opening angle of the resistance valve mounted on the reservoir module shown in Figure4a. The valve angle was adjusted from 90 degrees to 45 degrees over 5 steps, thereby reducing the open area ratio from 0.9 to 0.64. When the valve angle is 90 degrees, the area ratio is 0.9, the maximum, and the resistance is the minimum. As the valve angle decreases, the open area ratio decreases and the resistance increases. Figure9a shows pressure waveform according to area ratio. In the case of ventricular pressure, systolic pressure increases as peripheral resistance increases, diastolic pressure decreases, and as a result, peak-to-peak amplitude increases. In the case of aortic pressure, systolic pressure increases as peripheral resistance increases, diastolic pressure increases more, and as a result, peak-to-peak amplitude decreases. Figure9b shows the normalized aortic pressure waveform. To compare the pulse pressure, measured aortic pressures were normalized to the baseline aortic pressure in Figure8b, and shifted to have zero as the minimum value. As the valve angle decreases, the area ratio decreases and the peripheral resistance increases. At the same time, it can be seen that the pulse pressure decreases. This is consistent with the change in pulse pressure according to the peripheral resistance predicted through the simulation model of Figure7b. Therefore, the mock circulatory platform of this

Appl.studyAppl.Appl. Sci. Sci. Sci. can2020 2020 2020 reproduce, 10, 10, ,10 x, x,FOR xFOR FOR PEER PEER the PEER REVIEW blood REVIEW REVIEW pressure waveform according to the peripheral resistance. 1414 14of of 17of 17 17

(a(a)( )a ) (b(b)( b) )

FigureFigureFigure 9. 9. Experiment9. Experiment Experiment result result result according according according to to toresistance resistance resistance valve: valve: valve: ( a( (a )a( )measureda) measured) measured measured pressure pressure pressure pressure waveforms, waveforms, waveforms, : : :ventricular ventricular: ventricular pressure, pressure, pressure, :: : aortic aortic: aortic pressure; pressure; pressure; pressure; ( ( b(b ))( b)normalized normalized normalized) normalized aortic aorticaortic aortic pressure pressurepressure pressure waveform waveformwaveform waveform according according according to to to valvevalvevalve angle. angle. angle. 4.3. Parametric Study on Aortic Compliance 4.3.4.3.4.3. Parametric Parametric Parametric Study Study Study on on on Aortic Aortic Aortic Compliance Compliance Compliance ParametricParametricParametric studies studies studies of of ofaortic aortic aortic compliance compliance compliance were were were performed performed performed experimentally. experimentally. experimentally. In In In Inthis this this paper, paper, paper, aortic aortic aortic compliancecompliancecompliance is is controlledis controlled controlled by by by pressurization pressurization pressurization of of ofthe the the compliance compliance compliance compliance chamber chamber chamber chamber applied applied applied applied to to to tothe the the the ascending ascending ascending ascending aorta. aorta. aorta. aorta. TheTheThe pressurized pressurized pressurized additional additional additional pressure pressurepressure pressure was waswas was adjusted adjustedadjusted adjusted from fromfrom from 3.2 3.23.2 3.2 kPa kPakPa kPa to toto to14.3 14.314.3 14.3 kPa kPakPa kPa over overover over 5 55 steps. 5steps.steps. steps. The The The air air air inside inside inside thethethe compliance compliance compliance chamber chamber chamber pressurizes pressurizes pressurizes the the the ascending ascending ascending aorta aorta aorta with with with a a pressurizing apressurizing pressurizing cylinder cylinder cylinder and and and indirectly indirectly indirectly increasesincreasesincreases the the the sti stiffness stiffness ff stiffnessness of of theof of the the vascular the vascular vascular vascular wall. wall. wall. Therefore, wall. Therefore, Therefore, Therefore, as additional as as as additional additional additional pressure pressure pressure pressureincreases, increases, increases, increases, stiffness stiffnessincreases, stiffness stiffness increases,andincreases,increases, inversely, and and and inversely, complianceinversely, inversely, compliance compliance decreases.compliance decreases. In decreases. decreases. addition, In In the Inaddition, addition, methodaddition, the ofthe the directly method method method pressurizing of of ofdirectly directly directly pressurizing thepressurizing pressurizing fluid, the the way the the fluid,existingfluid,fluid, the the the cardiovascularway way way existing existing existing cardiovascular cardiovascular cardiovascular simulators control simulators simulators simulators compliance, control control control compliance, was compliance, compliance, compared was was was with. compared compared compared This is with. with. the with. sameThis This This is asis theis the the samemethodsamesame as as asthe the of the adjustingmethod method method of of the ofadjusting adjusting adjusting minimum the the the pressureminimum minimum minimum through pressure pressure pressure the through through reservoir through the the the in rese rese the reservoir mockrvoirrvoir in in circulatory inthe the the mock mock mock circulatory platformcirculatory circulatory of platformthisplatformplatform study, of of of andthis this this isstudy, study, hereinafterstudy, and and and is is referredishereinafter hereinafter hereinafter to asreferred referred thereferred reservoir to to toas as asthe method.the the reservoir reservoir reservoir The method. reservoirmethod. method. The The method The reservoir reservoir reservoir also method adjusted method method the minimum pressure from 40 mmHg to 40 mmHg over 5 steps. alsoalsoalso adjusted adjusted adjusted the the the minimum minimum minimum pressure pressure −pressure from from from −40 −40 −40 mmHg mmHg mmHg to to to40 40 40 mmHg mmHg mmHg over over over 5 5 steps. 5steps. steps. Figure 10a shows the pressure waveform according to the minimum pressure of the reservoir method,FigureFigureFigure which 10a 10a 10a shows isshows shows how the the the pressure existingpressure pressure cardiovascularwaveform waveform waveform according according according simulator to to tothe the controlsthe minimum minimum minimum compliance. pressure pressure pressure Asof of of athe the resultthe reservoir reservoir reservoir of the method,experiment,method,method, which which which as theis is ishow minimumhow how the the the existing existing existing pressure cardiovascular cardiovascular cardiovascular of the reservoir simulator simulator increased,simulator controls controls diastoliccontrols compliance. compliance. pressurecompliance. and As As As systolic a a result aresult result pressure of of ofthe the the experiment,experiment,experiment, as as as the the the minimum minimum minimum pressure pressure pressure of of of the the the reservoir reservoir reservoir increased, increased, increased, diastolic diastolic diastolic pressure pressure pressure and and and systolic systolic systolic pressurepressurepressure increased increased increased in in inboth both both the the the ventricle ventricle ventricle and and and the the the aorta. aorta. aorta. The The The amount amount amount of of ofdiastolic diastolic diastolic and and and systolic systolic systolic growth growth growth is is is similarsimilarsimilar and and and appears appears appears to to tomove move move parallel. parallel. parallel. Figure Figure Figure 10b 10b 10b shows shows shows the the the normalized normalized normalized aortic aortic aortic pressure pressure pressure waveforms. waveforms. waveforms. ToToTo compare compare compare the the the pulse pulse pulse pressures, pressures, pressures, measured measured measured aortic aortic aortic pressures pressures pressures were were were normalized normalized normalized to to tot het hethe baseline baseline baseline aortic aortic aortic pressurepressurepressure inin in Figure Figure Figure 8 8b b 8, ,b and, and and shifted shifted shifted to to to have have have zero zero zero as as as the the the minimum minimum minimum pressure. pressure. pressure. Theoretically, Theoretically, Theoretically, as as as the the the minimumminimumminimum pressure pressure pressure of of of the the the reservoir reservoir reservoir increases, increases, increases, the the the fluid fluid fluid inside inside inside the the the blood blood blood vessel vessel vessel is is is indirectly indirectly indirectly pressurized,pressurized,pressurized, the the the stiffness stiffness stiffness applied applied applied to to tothe the the fluid fluid fluid i ncreases,i ncreases,increases, and and and it it canit can can be be be predicted predicted predicted that that that the the the compliance compliance compliance decreases.decreases.decreases. According According According to to tothe the the simulation simulation simulation model model model in in inFigure Figure Figure 7c, 7c, 7c, it it canit can can be be be predicted predicted predicted that that that the the the pulse pulse pulse pressure pressure pressure willwillwill increase. increase. increase. However, However, However, as as asa a result aresult result of of ofthe the the experiment, experiment, experiment, pulse pulse pulse pressure pressure pressure decreased decreased decreased according according according to to toincrea increa increasessesses inin in thethe the minimum minimum minimum pressure pressure pressure of of of the the the reservoir. reservoir. reservoir. This This This is is is the the the opposite opposite opposite of of of the the the change change change in in in pulse pulse pulse pressure pressure pressure accordingaccordingaccording to to tothe the the aortic aortic aortic compliance compliance compliance predicted predicted predicted through through through the the the simulation simulation simulation model. model. model. Appl. Sci. 2020, 10, 5433 14 of 17 increased in both the ventricle and the aorta. The amount of diastolic and systolic growth is similar and appears to move parallel. Figure 10b shows the normalized aortic pressure waveforms. To compare the pulse pressures, measured aortic pressures were normalized to the baseline aortic pressure in Figure8b, and shifted to have zero as the minimum pressure. Theoretically, as the minimum pressure of the reservoir increases, the fluid inside the blood vessel is indirectly pressurized, the stiffness applied to the fluid increases, and it can be predicted that the compliance decreases. According to the simulation model in Figure7c, it can be predicted that the pulse pressure will increase. However, as a result of the experiment, pulse pressure decreased according to increases in the minimum pressure of the reservoir. This is the opposite of the change in pulse pressure according to the aortic compliance predicted through the simulation model. Appl.Appl. Sci. Sci. 2020 2020,, 10, 10,, x,x x FORFOR FOR PEERPEER PEER REVIEWREVIEW REVIEW 1515 of of 17 17

(a(a) ) (b(b) )

(c(c) ) (d(d) )

FigureFigure 10. 10. 10. ExperimentExperimentExperiment result result according according to to aortic aortic aortic compliance:compliance:compliance: ( a (a)) ) measured measured measured pressure pressure pressure waveforms waveforms waveforms waveforms accordingaccording to to minimum minimum pressure pressure of of the the reservoir reservoir reservoir method, method, method, ::: ventricular: ventricular ventricular pressure,pressure, pressure, ::: aortic: aortic aortic pressure;pressure;pressure; (( bb(b)) ) normalizednormalizednormalized normalized aorticaortic aortic pressurepressure pressure waveform waveform accordingaccording according to to to minimumminimum minimum pressure pressure pressure of of of thethe the reservoirreservoir reservoir method;method; ( c()c) ) measuredmeasured measured pressureprespres pressuresure waveformswaveforms waveforms accordingaccording according to to additionaladditional additional pressure pressure ofof of thethe the newnew new compliancecompliance compliance chamber,chamber,chamber, ::: : ventricular ventricular ventricular pressure, pressure, pressure, ::: : aortic aortic aortic pressure; pressure; pressure; ( (d (d)) ) normalized normalized normalized aortic aortic aortic pressure pressure pressure waveformwaveformwaveform accordingaccording according toto to additionaladditional additional pressurepressure pressure ofof of thethe the newnew new compliancecompliance compliance chamber.chamber. chamber.

FigureFigure 1010c 10cc showsshows shows the the pressure pressure waveformwaveform waveform accordingaccording according toto to thethe the additionaladditional additional pressure.pressure. pressure. As As a a result result of of the the experiment,experiment, diastolic diastolic and and systolic systolic blood blood pressure pressure increased increased in in both both the the ventricle ventricle and and the the aorta aorta as as the the additionaladditional pressure pressure inin in thethe the compliance compliance chamber chamber increased. increased. The The increase increase in in systo systolicsystolicliclic pressure pressure pressure is is is greater greater greater thanthanthan thethe the increase increase inin in diastolicdiastolic diastolic pressure,pressure, pressure, resultingresulting resulting inin in anan an increaseincrease increase inin in peak-to-peakpeak peak-to-to-peak-peak amplitude.amplitude. amplitude. Figure Figure 1010d 10dd showsshows a a a normalized normalized normalized aortic aortic pressure pressure waveform. waveform. waveform. To To To compare compare the the pulse pulse pressure, pressure, measured measured measured aortic aortic aortic pressurespressurespressures werewere were normalizednormalized normalized to to to the the the baseline bas baselineeline aortic aortic aortic pressure pressure pressure in in Figurein Figure Figure8b, 8 and8bb,, ,andand and shifted shiftedshifted shifted to have toto to havehave have zero zerozero aszero the asas as thethe minimum minimum value. value. As As expected, expected, as as the the additional additional pressure pressure in in the the compliance compliance chamber chamber increases, increases, stiffnessstiffness of of the the vascular vascular wall wall increases increases indirectly, indirectly, and and compliance compliance decreases. decreases. As As a a result result of of th thee experiment,experiment, pulse pulse pressure pressure increased increased according according to to increasing increasing the the additional additional pressure pressure of of the the compliancecompliance chamber. chamber. This This is is consistent consistent with with the the change change in in pulse pulse pressure pressure according according to to the the aortic aortic compliancecompliance predicted predicted through through the the simulation simulation model model in in Figure Figure 7c. 7c. T Therefore,herefore, the the mock mock circulatory circulatory platformplatform of of this this study study can can reproduce reproduce the the blood blood pressure pressure waveform waveform according according to to aortic aortic compliance compliance by by applyingapplying a a new new compliance compliance chamber. chamber.

5.5. Conclusions Conclusions InIn this this study, study, the the new new mock mock circulatory circulatory platform platform was was designed, designed, fabricated fabricated and and evaluated evaluated to to overcomeovercome the the limitations limitations that that existing existing simulators simulators do do not not reflect reflect the the actual actual physiology physiology of of the the cardiovascularcardiovascular system. system. The The new new mock mock circulatory circulatory platform platform was was designed designed b basedased on on the the physiology physiology of of eacheach component, component, whose whose key key parameters parameters such such as as resistance resistance and and compliance compliance can can be be adjusted. adjusted. From From the the Appl. Sci. 2020, 10, 5433 15 of 17 minimum value. As expected, as the additional pressure in the compliance chamber increases, stiﬀness of the vascular wall increases indirectly, and compliance decreases. As a result of the experiment, pulse pressure increased according to increasing the additional pressure of the compliance chamber. This is consistent with the change in pulse pressure according to the aortic compliance predicted through the simulation model in Figure7c. Therefore, the mock circulatory platform of this study can reproduce the blood pressure waveform according to aortic compliance by applying a new compliance chamber.

5. Conclusions In this study, the new mock circulatory platform was designed, fabricated and evaluated to overcome the limitations that existing simulators do not reflect the actual physiology of the cardiovascular system. The new mock circulatory platform was designed based on the physiology of each component, whose key parameters such as resistance and compliance can be adjusted. From the evaluation through the simulation model and experimental measurements, the mock circulatory platform can effectively reproduce the blood pressure waveform close to the Wiggers diagram, which represents the human body standard. In addition, parametric studies on the aortic compliance and the peripheral resistance were performed. The fabricated mock circulatory platform showed very close pressure waveforms in both cases of the simulation model and experimental measurement results. A new method for controlling the compliance of the aorta was suggested in this study. Previous studies have regulated the compliance by pressurizing the fluid with an air spring, increasing the pressure of the entire system but not actually the changing the compliance. On the other hand, the new compliance chamber exerts the pressure on the outer wall of the ascending aorta, changing the compliance of the wall. The result showed the same trend as in the simulation model, implying that the mock circulatory platform of this study can reproduce blood pressure waveforms based on the physiology of each component. The designed platform can generate a controllable pressure waveform based on the physiology of the cardiovascular system, and it can be applied to test the accuracy of the blood pressure measurement devices. It can also be used as a haptic actuator/simulator for palpation training. The platform of this study can be applied to the reproduction of various palpation feedbacks such as aortic waveforms that need to be carefully handled during surgery and femoral arterial waveforms during catheterization. However, except the ascending aorta of the proposed platform, other aortas are made of rigid acrylic, which has less compliance than the human body. In the future, the cardiovascular components other than the ascending aorta can be updated with flexible tubes and new compliance chambers in this study, to fully simulate the human cardiovascular system and reproduce the same or various blood pressure waveforms as in the Wiggers diagram. Based on the proposed platform, the brachial and radial arteries will be added for palpation training of healthcare professionals in future works.

Author Contributions: Conceptualization, Y.-M.K., J.K., S.-Y.W., T.-H.Y. and Y.-H.P.; methodology, T.-H.Y. and Y.-H.P.; software, J.-H.J. and T.-H.Y.; validation, B.L., J.H. and J.-H.J.; formal analysis, B.L., J.H. and J.-H.J.; investigation, B.L., J.H. and J.-H.J.; resources, B.L., T.-H.Y. and Y.-H.P.; data curation, B.L., J.H. and J.-H.J.; writing—original draft preparation, B.L. and J.-H.J.; writing—review and editing, T.-H.Y. and Y.-H.P.; visualization, B.L., J.-H.J., T.-H.Y. and Y.-H.P.; supervision, T.-H.Y. and Y.-H.P.; project administration, T.-H.Y. and Y.-H.P.; funding acquisition, Y.-M.K., J.K., S.-Y.W., T.-H.Y. and Y.-H.P. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Acknowledgments: This work was supported by “Human Resources Program in Energy Technology” of the Korea Institute of Energy Technology Evaluation and Planning (KETEP), granted financial resources from the Ministry of Trade, Industry & Energy, Republic of Korea. (No.20204030200050). This research was supported by a research grant (KSN2012110) from the Korea Institute of Oriental Medicine. Conflicts of Interest: The authors declare no conflict of interest. Appl. Sci. 2020, 10, 5433 16 of 17

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