Research ArticleTheHemodynamic Effect of Enhanced External CounterpulsationTreatment on Atherosclerotic Plaque in the Carotid Artery AFramework of Patient-Specific Computational FluidDynamics Analysis

Jianhang Du 123 Guangyao Wu 4 Bokai Wu5 Chang Liu5 Zhouming Mai12

Yumeng Liu5 Yawei Wang6 Pandeng Zhang5 Guifu Wu 123 and Jia Liu 57

1Department of Cardiology e Eighth Affiliated Hospital of Sun Yat-sen University Shenzhen 518033 China2Guangdong Innovative Engineering and Technology Research Center for Assisted Circulation (Sun Yat-sen University)Shenzhen 518033 China3NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University) Guangzhou 510080 China4Department of Radiology Shenzhen University General Hospital Shenzhen 518055 China5Laboratory for Engineering and Scientific Computing Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences Shenzhen 518055 China6School of Biological Science and Medical Engineering Beihang University Beijing 100083 China7Shenzhen Key Laboratory for Exascale Engineering and Scientific Computing Shenzhen China

Correspondence should be addressed to Guifu Wu wuguifumailsysueducn and Jia Liu jialiusiataccn

Received 7 June 2019 Revised 18 September 2019 Accepted 21 January 2020 Published 30 April 2020

Academic Editor Panagiotis Korantzopoulos

Copyright copy 2020 Jianhang Du et al is is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Long-term enhanced external counterpulsation (EECP) therapy has been recommended for antiatherogenesis in recent clinical ob-servations and trials However the precisemechanism underlying the benefits has not been fully clarified To quantify the effect of EECPintervention on arterial hemodynamic environment a framework of numerical assessment was introduced using a parallel computingalgorithm A 3D endothelial surface of the carotid artery with mild atherosclerotic plaque was constructed from images of magneticresonance angiography (MRA) Physiologic boundary conditions were derived from images of the ultrasound flow velocity spectrummeasured at the common carotid artery and before and during EECP intervention Hemodynamic factors relating to wall shear stress(WSS) and its spatial and temporal fluctuations were calculated and analyzed which included AWSS OSI and AWSSGMeasuring andcomputational results showed that diastole blood pressure perfusion andWSS level in carotid bifurcation were significantly increasedduring EECP intervention Mean AWSS level throughout the model increased by 169 while OSI level did not show a significantchange during EECPWe thus suggested that long-termEECP treatmentmight inhibit the initiation and development of atheroscleroticplaque via improving the hemodynamic environment in the carotid artery Meanwhile EECP performance induced a 196 increase inAWSSG level and whether it would influence the endothelial functions may need a further study Moreover the numerical methodproposed in this study was expected to be useful for the instant assessment of clinical application of EECP

1 Introduction

As a kind of noninvasive and atraumatic assisted circulationprocedure enhanced external counterpulsation (EECP) hasexhibited itself to be an effective safe and economical therapy inclinics for the management of ischemic cardiovascular and

cerebrovascular diseases in the recent decades [1ndash5] and hasbeen thought providing a better choice for patients with chronicstable angina who failed to respond to standard revasculari-zation procedures and aggressive pharmacotherapy [6]

e treatment of EECP (see Figure 1) involves the use ofan EECP device to inflate and deflate a series of

HindawiCardiology Research and PracticeVolume 2020 Article ID 5903790 12 pageshttpsdoiorg10115520205903790

compressive cuffs wrapped around the patientrsquos calveslower thighs and upper thighs As a result the enhancedflow perfusion is achieved from the devicersquos propellingblood from veins of the lower body to arteries of the upperbody and increases the blood supply for the importantorgans and the brain [7]

Long-term EECP intervention has been demonstratedin recent studies to be able to improve the endothelialfunctions and in turn may inhibit the generation anddevelopment of atherosclerosis lesion [8ndash11] e he-modynamic effects especially the wall shear stress vari-ations induced by EECP have been thought contributingthe most important part of its benefits Michaels et al [12]confirmed that EECP treatment could significantly in-crease coronary artery flow determined by both Dopplerand angiographic techniques Braith et al [10] suggestedthat EECP had a beneficial effect on peripheral arteryflow-mediated dilation and endothelial-derived vasoac-tive agents Our previous study [8] experimentally con-firmed that EECP inhibits intimal hyperplasia andatherogenesis by modifying biomechanical stress-re-sponsive gene expression However the actual influenceof EECP intervention on wall shear stress (WSS) and itsspatial and temporary fluctuations remained elusive

It has been widely accepted that biomechanical stressesof large and medium arteries play an important role inmaintaining the functions of endothelium and vascularremodeling progression [13] Low andor oscillating WSShas been commonly believed to be correlated positivelywith initiation and development of atherosclerosis [14ndash16]Several hemodynamic factors have been proposed by dif-ferent research groups to represent the biomechanicalindicators connected to arterial functions such as averagewall shear stress (AWSS) oscillatory shear index (OSI)particle resident time (PRT) and wall shear stress gradient(WSSG)

is paper was aimed to conduct a pilot study on how theEECP treatment affects the hemodynamic environment andthe important factors in carotid arterial bifurcation wherethe atherosclerotic lesion localizes characteristically A nu-merical method-combined finite element method with in

vivomedical imaging measurement was introduced to assessthe local hemodynamic factors during EECP intervention

2 Medical Image Acquisition and Processing

A 55-year-old coronary heart disease patient with mildcarotid atheromatous plaque diagnosed (severity of stenosiswas less than 20) was enrolled to the measurement esubject underwent the clinical protocol for carotid plaqueMRI on a 3T MRI (General Electric Company DiscoveryMR750) A two-element bilateral 8-channel carotid surfacecoil (Wk401 Jiangyin Wankang Medical Technology CoLtd) was used for image acquisition

A three-dimensional phase-contrast magnetic resonanceangiography (3D Phase Contrast) sequence was performedrepetition timeecho time (TRTE) 15037ms flip angle 8degfield of view 32 cmtimes 32 cm slice thickness 18mm andmatrix 384times 256 A High Resolution ree-DimensionalCUBE (computer use by engineers) T1 Weighted Imag-ing(HR 3D CUBE T1WI) sequence was performed as fol-lows repetition timeecho time (TRTE) 57515ms echochain length (ETL) 24 slice thickness 08mm field of view28 cmtimes 28 cm and matrix 256times 256)

3 EECP Intervention Protocol and ColorDoppler Ultrasound Measurement

A short-term EECP intervention was performed using Push-ikang P-ECPTM Oxygen Saturation Monitoring EnhancedExternal Counterpulsation Instrument (made in ChongqingChina) e subject received a single 45-minute session EECPtreatment with the working pressure set to 0033MPa

e blood velocity measurements of before EECP (reststate) and during EECP (15-25min after EECP initiated)were performed based on a Color Doppler UltrasoundSystem (Philip EPIQ7) (see Figure 2) e left commoncarotid arteries (CCA) were examined with 15 cm proximalto the bifurcation of the vessels e blood velocity wave-forms (see Figure 3) in cardiac cycles and before and duringEECP intervention were extracted from the images of ultra-sound flow velocity spectrum Meanwhile the diameterchanges of the lumen section (see Figure 4) in cardiac cycleswere extracted from images of ultrasounde blood flow ratein cardiac cycle and perfusion in CCA could be calculatedbased on velocity waveforms and diameter changes

4 3D Reconstruction for the EndothelialSurface of the Carotid Artery

We propose a method to virtually reconstruct the endo-thelial surface of the carotid artery so as to visualize thecarotid atheromatous plaque in 3De pipeline of our workis shown in Figure 5 where It denotes the input MR imagewith index t t 1 2 3 Pt represents the artery endo-thelial boundary extracted from It is pipeline consists ofthree main steps image preprocessing endothelial boundaryextraction and 3D reconstruction

Figure 1 EECP treatment in clinics and animal experiment [6]e technique involves the using of a set of cuffs that are wrappedaround the lower parts of the body and connected to an aircompressor with tubes

2 Cardiology Research and Practice

5 Image Preprocessing

ere exists serious inherent noise in theMR image as shownin Figure 6(a) e noise has a detrimental influence on theaccuracy of the artery extraction and 3D reconstruction Inorder to reduce the noise without affecting the shape of thecarotid artery we make use of the morphological techniquecalled open-by-reconstruction and close-by-reconstruction

[17]e processed result is illustrated in Figure 6(b) It can beseen that most of the clutters in Figure 6(a) have been re-moved and the shape of the carotid artery is not influenced

51 Endothelial Boundary Extraction e extraction of theendothelial boundary of the carotid artery in each MRAimage is implemented based on the result of image

(a) (b)

Figure 2 Blood flow velocity and spectrum measurement based on Color Doppler Ultrasound (a) pre-EECP intervention (b) DuringEECP intervention Note that EECP significantly changed the blood flow pattern and increased the blood flow level in diastole

Pre-EECPDuring EECP

0

20

40

60

80

100

120

140

Velo

city

(cm

s)

01 02 03 04 05 06 07 080Time (s)

Figure 3 Blood velocity waveforms at CCA in a cardiac cycle before and during EECP which were extracted from the images of ultrasoundflow velocity spectrum

Pre-EECPDuring EECP

00102030405060708

Dia

met

er o

f lum

en (c

m)

01 02 03 04 05 06 07 080Time (s)

Figure 4 Diameter of the lumen at CCA in a cardiac cycle before and during EECP which were extracted from the images of ultrasoundcarotid artery

Cardiology Research and Practice 3

preprocessing For t= 1 we manually extract the boundaryof the carotid artery in I1 so as to initialize the subsequentautomatic extraction If tgt 1 given the extraction result Ptminus1(the yellow curve in Figure 7(a))we first binarize the Itpreprocessed and then obtain the edge map E from thisbinary image (Figure 7(b)) Because of the great similar-ity between It and Itminus1 we eventually optimize a closed curvec= [x y] which satisfies the following equation with calculusof variations using Ptminus1 as the initial value

min1113929 αdc(s)

ds

2

+ β

d2c(s)

ds2

2

+ c(1 minus E(x(s) y(s)))ds

(1)

where s is the arc parameter of c and α β as well as c are thethree scalars to balance the three terms in equation (1) eoptimized c is the result Pt of It as shown by the yellow curvein Figure 7(c) Equation (1) can be calculated by the methodproposed in [18]

52 Texture Flattening and 3D Reconstruction e carotidartery can be approximately considered as a surface of revolution(SOR) Providing that the endothelial boundary of the carotidartery in each MRI slice has been extracted the algorithmproposed in [19] can be adopted to flatten the texture of theendothelial surface of the carotid artery and then generate a 3Dtexture reconstruction for the endothelial surface e carotidartery will bifurcate at its end so we can generate the 3D texturereconstruction for each bifurcation by the same way and finallycombine all reconstructions togethere final reconstruction of

the carotid artery is demonstrated in Figure 8 In this figure thedark and concave region is the carotid atherosclerotic plaque

6 The CFD Method and theBoundary Conditions

61 Geometry and Boundary Conditions To simplify sim-ulations the elasticity of vessel wall is not considered in thepresent study (ie computational domain was fixed)Original geometry consists of four boundaries inlet outletand wall An artificial extension geometry with a length of 5times the averaged radius of the inlet is added outward alongthe normal direction of the inlet boundary to acquire a fullydeveloped velocity waveform [15] as depicted in Figure 9Inflow velocity (Vin) measured by the carotid Doppler (seeFigure 3) is specified at the inlet_ex Opening condition is setat the outlet and wall is assumed to be no-slip

62 Mesh Generation Most part of the geometry is meshedwith tetrahedral cells by employing the commercial softwareANSYS ICEM (ANSYS Inc USA) To capture the flowbehavior where high velocity gradient exists inflation layersare created near the wall [16] (as shown in Figure 10) Tooptimize the mesh size a specific mesh-independent study iscarried out for reliable results while keeping computationalloads as low as possible As indicated in Table 1 change inAWSS is around 3with refinement fromMesh 1 toMesh 3while less than 1 from Mesh 3 to Mesh 4 for both stateswith and without EECP Mesh used in this study is ofquantity 720085 (ie Mesh 3) and with a quality of sim04

Endothelial boundary extraction

Image preprocessingCT image It t gt 1Automatic artery

endothelial boundaryextraction

Manual arteryendothelial boundary

extraction

Result Pt

Texture flattening and 3Dreconstruction

Pt t = 1 2 3 3D carotid artery

N

Y

Figure 5 e pipeline of our algorithm

(a) (b)

Figure 6 (a) e original MR image (b) e result of morphological reconstruction

4 Cardiology Research and Practice

(measured by its orthogonality and warpage) which is at anacceptable level

63 Rheology andGoverningEquations e blood fluid usedin the present study is assumed to be impressible and iso-viscous (ie Newtonian type) erefore the governingtransport equations for this study are continuity and mo-mentum equations which can be written in their generalforms [20] as follows

continuity nabla middot v 0 (2)

momentumzv

zt+(v middot nabla)v minus

1ρnablap +

μρnabla2v + f (3)

where ] is the velocity vector p is the pressure ρ is the fluiddensity and f is the external force (assumed to be 0 here)

Original geometryExtension geometry

Inlet_ex

Outlet2

Outlet1WallOutlet_exinletWall_ex

05

10 20 (mm) 15

Figure 9 Geometry and boundaries of the carotid artery

Figure 10 Schematic mesh at the inlet

Carotid atherosclerotic plaque

0

5

10

15

20

25

2520

15 130135

(mm)

(mm

)

Figure 8 e reconstruction of the carotid artery

(a) (b) (c)

Figure 7 Automatic endothelial boundary extraction (a) e result Ptminus1 (b) e edge map of the binarized It (c) e result Pt

Cardiology Research and Practice 5

64e solver egoverning equations are discretized by CFXcode based on a finite-volumemethod Tomeet the requirementon both robustness and accuracy a so-called ldquoHigh ResolutionAdvection Schemerdquo is implemented in this study [21] Nu-merical solutions are acquired while root mean square (RMS) ofboth mass and momentum residuals are below 10minus5 In facthowever at most time steps even lower RMS residual values aregenerally reached We solve the unknowns with this

configuration for four cardiac cycles Results of the last cardiaccycle are presented in the following section

7 Results

Several important hemodynamic factors such as AWSSOSI RRT and WSSG were calculated in this paper whichwere introduced by different research groups to represent

Relative pressure(Pa)

0

40

80

120

160

200

240

280

320

360

0

25

5

75

10(mm)

(a)

Relative pressure(Pa)

0

250

500

750

1000

1250

1500

1750

2000

2250

0

25

5

75

10(mm)

(b)

Figure 11 Relative blood pressure distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP in-tervention significantly increased the blood pressure in diastole

Table 1 Results of specific mesh-independent study

Mesh 1 Mesh 2 Mesh 3 Mesh 4Mesh quantity 259706 419466 720085 907589AWSS (Pa) (pre-EECP) 7772 7921 7966 7991AWSS (Pa) (during EECP) 9043 9236 9359 9372

6 Cardiology Research and Practice

the WSS level in a cardiac cycle and its spatial and tem-porary fluctuation ese factors are defined as follows[22 23]

AWSS 1T

1113946T

0τrarrw

11138681113868111386811138681113868111386811138681113868dt (4)

WSSG

z τrarrw

zx

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zy

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zz

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

11139741113972

(5)

AWSSG 1T

1113946T

0WSSGdt (6)

OSI 12

1 minus1113938

T

0 τrarrwdt11138681113868111386811138681113868

11138681113868111386811138681113868

1113938T

0 τrarrw

11138681113868111386811138681113868111386811138681113868dt

⎛⎝ ⎞⎠ (7)

RRT 1

(1 minus 2OSI) times AWSS (8)

where | τrarrw| is the magnitude of the instantaneous WSSvector τrarrw and T is the cardiac cycle

e numerical results are shown in Figures 11ndash15Focus of previous studies were mainly put on how EECPaffected the blood flow and pressure in diastole [1 12] Inthe current paper the velocity and pressure at time pointsof t 054T and t 058T were chosen to represent theblood velocity and pressure in diastole before and during

Velocity streamline (ms)

00

0375

075

1125

1 5

25

0 5

75

10(mm)

(a)

25

0 5

75

10(mm)

Velocity streamline (ms)

00

0375

075

1125

1 5

(b)

Figure 12 Blood velocity distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP interventionsignificantly increased the blood velocity in diastole

Cardiology Research and Practice 7

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

5 Image Preprocessing

ere exists serious inherent noise in theMR image as shownin Figure 6(a) e noise has a detrimental influence on theaccuracy of the artery extraction and 3D reconstruction Inorder to reduce the noise without affecting the shape of thecarotid artery we make use of the morphological techniquecalled open-by-reconstruction and close-by-reconstruction

[17]e processed result is illustrated in Figure 6(b) It can beseen that most of the clutters in Figure 6(a) have been re-moved and the shape of the carotid artery is not influenced

51 Endothelial Boundary Extraction e extraction of theendothelial boundary of the carotid artery in each MRAimage is implemented based on the result of image

(a) (b)

Figure 2 Blood flow velocity and spectrum measurement based on Color Doppler Ultrasound (a) pre-EECP intervention (b) DuringEECP intervention Note that EECP significantly changed the blood flow pattern and increased the blood flow level in diastole

Pre-EECPDuring EECP

0

20

40

60

80

100

120

140

Velo

city

(cm

s)

01 02 03 04 05 06 07 080Time (s)

Figure 3 Blood velocity waveforms at CCA in a cardiac cycle before and during EECP which were extracted from the images of ultrasoundflow velocity spectrum

Pre-EECPDuring EECP

00102030405060708

Dia

met

er o

f lum

en (c

m)

01 02 03 04 05 06 07 080Time (s)

Figure 4 Diameter of the lumen at CCA in a cardiac cycle before and during EECP which were extracted from the images of ultrasoundcarotid artery

Cardiology Research and Practice 3

preprocessing For t= 1 we manually extract the boundaryof the carotid artery in I1 so as to initialize the subsequentautomatic extraction If tgt 1 given the extraction result Ptminus1(the yellow curve in Figure 7(a))we first binarize the Itpreprocessed and then obtain the edge map E from thisbinary image (Figure 7(b)) Because of the great similar-ity between It and Itminus1 we eventually optimize a closed curvec= [x y] which satisfies the following equation with calculusof variations using Ptminus1 as the initial value

min1113929 αdc(s)

ds

2

+ β

d2c(s)

ds2

2

+ c(1 minus E(x(s) y(s)))ds

(1)

where s is the arc parameter of c and α β as well as c are thethree scalars to balance the three terms in equation (1) eoptimized c is the result Pt of It as shown by the yellow curvein Figure 7(c) Equation (1) can be calculated by the methodproposed in [18]

52 Texture Flattening and 3D Reconstruction e carotidartery can be approximately considered as a surface of revolution(SOR) Providing that the endothelial boundary of the carotidartery in each MRI slice has been extracted the algorithmproposed in [19] can be adopted to flatten the texture of theendothelial surface of the carotid artery and then generate a 3Dtexture reconstruction for the endothelial surface e carotidartery will bifurcate at its end so we can generate the 3D texturereconstruction for each bifurcation by the same way and finallycombine all reconstructions togethere final reconstruction of

the carotid artery is demonstrated in Figure 8 In this figure thedark and concave region is the carotid atherosclerotic plaque

6 The CFD Method and theBoundary Conditions

61 Geometry and Boundary Conditions To simplify sim-ulations the elasticity of vessel wall is not considered in thepresent study (ie computational domain was fixed)Original geometry consists of four boundaries inlet outletand wall An artificial extension geometry with a length of 5times the averaged radius of the inlet is added outward alongthe normal direction of the inlet boundary to acquire a fullydeveloped velocity waveform [15] as depicted in Figure 9Inflow velocity (Vin) measured by the carotid Doppler (seeFigure 3) is specified at the inlet_ex Opening condition is setat the outlet and wall is assumed to be no-slip

62 Mesh Generation Most part of the geometry is meshedwith tetrahedral cells by employing the commercial softwareANSYS ICEM (ANSYS Inc USA) To capture the flowbehavior where high velocity gradient exists inflation layersare created near the wall [16] (as shown in Figure 10) Tooptimize the mesh size a specific mesh-independent study iscarried out for reliable results while keeping computationalloads as low as possible As indicated in Table 1 change inAWSS is around 3with refinement fromMesh 1 toMesh 3while less than 1 from Mesh 3 to Mesh 4 for both stateswith and without EECP Mesh used in this study is ofquantity 720085 (ie Mesh 3) and with a quality of sim04

Endothelial boundary extraction

Image preprocessingCT image It t gt 1Automatic artery

endothelial boundaryextraction

Manual arteryendothelial boundary

extraction

Result Pt

Texture flattening and 3Dreconstruction

Pt t = 1 2 3 3D carotid artery

N

Y

Figure 5 e pipeline of our algorithm

(a) (b)

Figure 6 (a) e original MR image (b) e result of morphological reconstruction

4 Cardiology Research and Practice

(measured by its orthogonality and warpage) which is at anacceptable level

63 Rheology andGoverningEquations e blood fluid usedin the present study is assumed to be impressible and iso-viscous (ie Newtonian type) erefore the governingtransport equations for this study are continuity and mo-mentum equations which can be written in their generalforms [20] as follows

continuity nabla middot v 0 (2)

momentumzv

zt+(v middot nabla)v minus

1ρnablap +

μρnabla2v + f (3)

where ] is the velocity vector p is the pressure ρ is the fluiddensity and f is the external force (assumed to be 0 here)

Original geometryExtension geometry

Inlet_ex

Outlet2

Outlet1WallOutlet_exinletWall_ex

05

10 20 (mm) 15

Figure 9 Geometry and boundaries of the carotid artery

Figure 10 Schematic mesh at the inlet

Carotid atherosclerotic plaque

0

5

10

15

20

25

2520

15 130135

(mm)

(mm

)

Figure 8 e reconstruction of the carotid artery

(a) (b) (c)

Figure 7 Automatic endothelial boundary extraction (a) e result Ptminus1 (b) e edge map of the binarized It (c) e result Pt

Cardiology Research and Practice 5

64e solver egoverning equations are discretized by CFXcode based on a finite-volumemethod Tomeet the requirementon both robustness and accuracy a so-called ldquoHigh ResolutionAdvection Schemerdquo is implemented in this study [21] Nu-merical solutions are acquired while root mean square (RMS) ofboth mass and momentum residuals are below 10minus5 In facthowever at most time steps even lower RMS residual values aregenerally reached We solve the unknowns with this

configuration for four cardiac cycles Results of the last cardiaccycle are presented in the following section

7 Results

Several important hemodynamic factors such as AWSSOSI RRT and WSSG were calculated in this paper whichwere introduced by different research groups to represent

Relative pressure(Pa)

0

40

80

120

160

200

240

280

320

360

0

25

5

75

10(mm)

(a)

Relative pressure(Pa)

0

250

500

750

1000

1250

1500

1750

2000

2250

0

25

5

75

10(mm)

(b)

Figure 11 Relative blood pressure distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP in-tervention significantly increased the blood pressure in diastole

Table 1 Results of specific mesh-independent study

Mesh 1 Mesh 2 Mesh 3 Mesh 4Mesh quantity 259706 419466 720085 907589AWSS (Pa) (pre-EECP) 7772 7921 7966 7991AWSS (Pa) (during EECP) 9043 9236 9359 9372

6 Cardiology Research and Practice

the WSS level in a cardiac cycle and its spatial and tem-porary fluctuation ese factors are defined as follows[22 23]

AWSS 1T

1113946T

0τrarrw

11138681113868111386811138681113868111386811138681113868dt (4)

WSSG

z τrarrw

zx

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zy

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zz

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

11139741113972

(5)

AWSSG 1T

1113946T

0WSSGdt (6)

OSI 12

1 minus1113938

T

0 τrarrwdt11138681113868111386811138681113868

11138681113868111386811138681113868

1113938T

0 τrarrw

11138681113868111386811138681113868111386811138681113868dt

⎛⎝ ⎞⎠ (7)

RRT 1

(1 minus 2OSI) times AWSS (8)

where | τrarrw| is the magnitude of the instantaneous WSSvector τrarrw and T is the cardiac cycle

e numerical results are shown in Figures 11ndash15Focus of previous studies were mainly put on how EECPaffected the blood flow and pressure in diastole [1 12] Inthe current paper the velocity and pressure at time pointsof t 054T and t 058T were chosen to represent theblood velocity and pressure in diastole before and during

Velocity streamline (ms)

00

0375

075

1125

1 5

25

0 5

75

10(mm)

(a)

25

0 5

75

10(mm)

Velocity streamline (ms)

00

0375

075

1125

1 5

(b)

Figure 12 Blood velocity distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP interventionsignificantly increased the blood velocity in diastole

Cardiology Research and Practice 7

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

preprocessing For t= 1 we manually extract the boundaryof the carotid artery in I1 so as to initialize the subsequentautomatic extraction If tgt 1 given the extraction result Ptminus1(the yellow curve in Figure 7(a))we first binarize the Itpreprocessed and then obtain the edge map E from thisbinary image (Figure 7(b)) Because of the great similar-ity between It and Itminus1 we eventually optimize a closed curvec= [x y] which satisfies the following equation with calculusof variations using Ptminus1 as the initial value

min1113929 αdc(s)

ds

2

+ β

d2c(s)

ds2

2

+ c(1 minus E(x(s) y(s)))ds

(1)

where s is the arc parameter of c and α β as well as c are thethree scalars to balance the three terms in equation (1) eoptimized c is the result Pt of It as shown by the yellow curvein Figure 7(c) Equation (1) can be calculated by the methodproposed in [18]

52 Texture Flattening and 3D Reconstruction e carotidartery can be approximately considered as a surface of revolution(SOR) Providing that the endothelial boundary of the carotidartery in each MRI slice has been extracted the algorithmproposed in [19] can be adopted to flatten the texture of theendothelial surface of the carotid artery and then generate a 3Dtexture reconstruction for the endothelial surface e carotidartery will bifurcate at its end so we can generate the 3D texturereconstruction for each bifurcation by the same way and finallycombine all reconstructions togethere final reconstruction of

the carotid artery is demonstrated in Figure 8 In this figure thedark and concave region is the carotid atherosclerotic plaque

6 The CFD Method and theBoundary Conditions

61 Geometry and Boundary Conditions To simplify sim-ulations the elasticity of vessel wall is not considered in thepresent study (ie computational domain was fixed)Original geometry consists of four boundaries inlet outletand wall An artificial extension geometry with a length of 5times the averaged radius of the inlet is added outward alongthe normal direction of the inlet boundary to acquire a fullydeveloped velocity waveform [15] as depicted in Figure 9Inflow velocity (Vin) measured by the carotid Doppler (seeFigure 3) is specified at the inlet_ex Opening condition is setat the outlet and wall is assumed to be no-slip

62 Mesh Generation Most part of the geometry is meshedwith tetrahedral cells by employing the commercial softwareANSYS ICEM (ANSYS Inc USA) To capture the flowbehavior where high velocity gradient exists inflation layersare created near the wall [16] (as shown in Figure 10) Tooptimize the mesh size a specific mesh-independent study iscarried out for reliable results while keeping computationalloads as low as possible As indicated in Table 1 change inAWSS is around 3with refinement fromMesh 1 toMesh 3while less than 1 from Mesh 3 to Mesh 4 for both stateswith and without EECP Mesh used in this study is ofquantity 720085 (ie Mesh 3) and with a quality of sim04

Endothelial boundary extraction

Image preprocessingCT image It t gt 1Automatic artery

endothelial boundaryextraction

Manual arteryendothelial boundary

extraction

Result Pt

Texture flattening and 3Dreconstruction

Pt t = 1 2 3 3D carotid artery

N

Y

Figure 5 e pipeline of our algorithm

(a) (b)

Figure 6 (a) e original MR image (b) e result of morphological reconstruction

4 Cardiology Research and Practice

(measured by its orthogonality and warpage) which is at anacceptable level

63 Rheology andGoverningEquations e blood fluid usedin the present study is assumed to be impressible and iso-viscous (ie Newtonian type) erefore the governingtransport equations for this study are continuity and mo-mentum equations which can be written in their generalforms [20] as follows

continuity nabla middot v 0 (2)

momentumzv

zt+(v middot nabla)v minus

1ρnablap +

μρnabla2v + f (3)

where ] is the velocity vector p is the pressure ρ is the fluiddensity and f is the external force (assumed to be 0 here)

Original geometryExtension geometry

Inlet_ex

Outlet2

Outlet1WallOutlet_exinletWall_ex

05

10 20 (mm) 15

Figure 9 Geometry and boundaries of the carotid artery

Figure 10 Schematic mesh at the inlet

Carotid atherosclerotic plaque

0

5

10

15

20

25

2520

15 130135

(mm)

(mm

)

Figure 8 e reconstruction of the carotid artery

(a) (b) (c)

Figure 7 Automatic endothelial boundary extraction (a) e result Ptminus1 (b) e edge map of the binarized It (c) e result Pt

Cardiology Research and Practice 5

64e solver egoverning equations are discretized by CFXcode based on a finite-volumemethod Tomeet the requirementon both robustness and accuracy a so-called ldquoHigh ResolutionAdvection Schemerdquo is implemented in this study [21] Nu-merical solutions are acquired while root mean square (RMS) ofboth mass and momentum residuals are below 10minus5 In facthowever at most time steps even lower RMS residual values aregenerally reached We solve the unknowns with this

configuration for four cardiac cycles Results of the last cardiaccycle are presented in the following section

7 Results

Several important hemodynamic factors such as AWSSOSI RRT and WSSG were calculated in this paper whichwere introduced by different research groups to represent

Relative pressure(Pa)

0

40

80

120

160

200

240

280

320

360

0

25

5

75

10(mm)

(a)

Relative pressure(Pa)

0

250

500

750

1000

1250

1500

1750

2000

2250

0

25

5

75

10(mm)

(b)

Figure 11 Relative blood pressure distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP in-tervention significantly increased the blood pressure in diastole

Table 1 Results of specific mesh-independent study

Mesh 1 Mesh 2 Mesh 3 Mesh 4Mesh quantity 259706 419466 720085 907589AWSS (Pa) (pre-EECP) 7772 7921 7966 7991AWSS (Pa) (during EECP) 9043 9236 9359 9372

6 Cardiology Research and Practice

the WSS level in a cardiac cycle and its spatial and tem-porary fluctuation ese factors are defined as follows[22 23]

AWSS 1T

1113946T

0τrarrw

11138681113868111386811138681113868111386811138681113868dt (4)

WSSG

z τrarrw

zx

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zy

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zz

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

11139741113972

(5)

AWSSG 1T

1113946T

0WSSGdt (6)

OSI 12

1 minus1113938

T

0 τrarrwdt11138681113868111386811138681113868

11138681113868111386811138681113868

1113938T

0 τrarrw

11138681113868111386811138681113868111386811138681113868dt

⎛⎝ ⎞⎠ (7)

RRT 1

(1 minus 2OSI) times AWSS (8)

where | τrarrw| is the magnitude of the instantaneous WSSvector τrarrw and T is the cardiac cycle

e numerical results are shown in Figures 11ndash15Focus of previous studies were mainly put on how EECPaffected the blood flow and pressure in diastole [1 12] Inthe current paper the velocity and pressure at time pointsof t 054T and t 058T were chosen to represent theblood velocity and pressure in diastole before and during

Velocity streamline (ms)

00

0375

075

1125

1 5

25

0 5

75

10(mm)

(a)

25

0 5

75

10(mm)

Velocity streamline (ms)

00

0375

075

1125

1 5

(b)

Figure 12 Blood velocity distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP interventionsignificantly increased the blood velocity in diastole

Cardiology Research and Practice 7

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

(measured by its orthogonality and warpage) which is at anacceptable level

63 Rheology andGoverningEquations e blood fluid usedin the present study is assumed to be impressible and iso-viscous (ie Newtonian type) erefore the governingtransport equations for this study are continuity and mo-mentum equations which can be written in their generalforms [20] as follows

continuity nabla middot v 0 (2)

momentumzv

zt+(v middot nabla)v minus

1ρnablap +

μρnabla2v + f (3)

where ] is the velocity vector p is the pressure ρ is the fluiddensity and f is the external force (assumed to be 0 here)

Original geometryExtension geometry

Inlet_ex

Outlet2

Outlet1WallOutlet_exinletWall_ex

05

10 20 (mm) 15

Figure 9 Geometry and boundaries of the carotid artery

Figure 10 Schematic mesh at the inlet

Carotid atherosclerotic plaque

0

5

10

15

20

25

2520

15 130135

(mm)

(mm

)

Figure 8 e reconstruction of the carotid artery

(a) (b) (c)

Figure 7 Automatic endothelial boundary extraction (a) e result Ptminus1 (b) e edge map of the binarized It (c) e result Pt

Cardiology Research and Practice 5

64e solver egoverning equations are discretized by CFXcode based on a finite-volumemethod Tomeet the requirementon both robustness and accuracy a so-called ldquoHigh ResolutionAdvection Schemerdquo is implemented in this study [21] Nu-merical solutions are acquired while root mean square (RMS) ofboth mass and momentum residuals are below 10minus5 In facthowever at most time steps even lower RMS residual values aregenerally reached We solve the unknowns with this

configuration for four cardiac cycles Results of the last cardiaccycle are presented in the following section

7 Results

Several important hemodynamic factors such as AWSSOSI RRT and WSSG were calculated in this paper whichwere introduced by different research groups to represent

Relative pressure(Pa)

0

40

80

120

160

200

240

280

320

360

0

25

5

75

10(mm)

(a)

Relative pressure(Pa)

0

250

500

750

1000

1250

1500

1750

2000

2250

0

25

5

75

10(mm)

(b)

Figure 11 Relative blood pressure distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP in-tervention significantly increased the blood pressure in diastole

Table 1 Results of specific mesh-independent study

Mesh 1 Mesh 2 Mesh 3 Mesh 4Mesh quantity 259706 419466 720085 907589AWSS (Pa) (pre-EECP) 7772 7921 7966 7991AWSS (Pa) (during EECP) 9043 9236 9359 9372

6 Cardiology Research and Practice

the WSS level in a cardiac cycle and its spatial and tem-porary fluctuation ese factors are defined as follows[22 23]

AWSS 1T

1113946T

0τrarrw

11138681113868111386811138681113868111386811138681113868dt (4)

WSSG

z τrarrw

zx

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zy

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zz

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

11139741113972

(5)

AWSSG 1T

1113946T

0WSSGdt (6)

OSI 12

1 minus1113938

T

0 τrarrwdt11138681113868111386811138681113868

11138681113868111386811138681113868

1113938T

0 τrarrw

11138681113868111386811138681113868111386811138681113868dt

⎛⎝ ⎞⎠ (7)

RRT 1

(1 minus 2OSI) times AWSS (8)

where | τrarrw| is the magnitude of the instantaneous WSSvector τrarrw and T is the cardiac cycle

e numerical results are shown in Figures 11ndash15Focus of previous studies were mainly put on how EECPaffected the blood flow and pressure in diastole [1 12] Inthe current paper the velocity and pressure at time pointsof t 054T and t 058T were chosen to represent theblood velocity and pressure in diastole before and during

Velocity streamline (ms)

00

0375

075

1125

1 5

25

0 5

75

10(mm)

(a)

25

0 5

75

10(mm)

Velocity streamline (ms)

00

0375

075

1125

1 5

(b)

Figure 12 Blood velocity distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP interventionsignificantly increased the blood velocity in diastole

Cardiology Research and Practice 7

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

64e solver egoverning equations are discretized by CFXcode based on a finite-volumemethod Tomeet the requirementon both robustness and accuracy a so-called ldquoHigh ResolutionAdvection Schemerdquo is implemented in this study [21] Nu-merical solutions are acquired while root mean square (RMS) ofboth mass and momentum residuals are below 10minus5 In facthowever at most time steps even lower RMS residual values aregenerally reached We solve the unknowns with this

configuration for four cardiac cycles Results of the last cardiaccycle are presented in the following section

7 Results

Several important hemodynamic factors such as AWSSOSI RRT and WSSG were calculated in this paper whichwere introduced by different research groups to represent

Relative pressure(Pa)

0

40

80

120

160

200

240

280

320

360

0

25

5

75

10(mm)

(a)

Relative pressure(Pa)

0

250

500

750

1000

1250

1500

1750

2000

2250

0

25

5

75

10(mm)

(b)

Figure 11 Relative blood pressure distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP in-tervention significantly increased the blood pressure in diastole

Table 1 Results of specific mesh-independent study

Mesh 1 Mesh 2 Mesh 3 Mesh 4Mesh quantity 259706 419466 720085 907589AWSS (Pa) (pre-EECP) 7772 7921 7966 7991AWSS (Pa) (during EECP) 9043 9236 9359 9372

6 Cardiology Research and Practice

the WSS level in a cardiac cycle and its spatial and tem-porary fluctuation ese factors are defined as follows[22 23]

AWSS 1T

1113946T

0τrarrw

11138681113868111386811138681113868111386811138681113868dt (4)

WSSG

z τrarrw

zx

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zy

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zz

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

11139741113972

(5)

AWSSG 1T

1113946T

0WSSGdt (6)

OSI 12

1 minus1113938

T

0 τrarrwdt11138681113868111386811138681113868

11138681113868111386811138681113868

1113938T

0 τrarrw

11138681113868111386811138681113868111386811138681113868dt

⎛⎝ ⎞⎠ (7)

RRT 1

(1 minus 2OSI) times AWSS (8)

where | τrarrw| is the magnitude of the instantaneous WSSvector τrarrw and T is the cardiac cycle

e numerical results are shown in Figures 11ndash15Focus of previous studies were mainly put on how EECPaffected the blood flow and pressure in diastole [1 12] Inthe current paper the velocity and pressure at time pointsof t 054T and t 058T were chosen to represent theblood velocity and pressure in diastole before and during

Velocity streamline (ms)

00

0375

075

1125

1 5

25

0 5

75

10(mm)

(a)

25

0 5

75

10(mm)

Velocity streamline (ms)

00

0375

075

1125

1 5

(b)

Figure 12 Blood velocity distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP interventionsignificantly increased the blood velocity in diastole

Cardiology Research and Practice 7

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

the WSS level in a cardiac cycle and its spatial and tem-porary fluctuation ese factors are defined as follows[22 23]

AWSS 1T

1113946T

0τrarrw

11138681113868111386811138681113868111386811138681113868dt (4)

WSSG

z τrarrw

zx

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zy

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

+z τrarrw

zz

11138681113868111386811138681113868111386811138681113868

111386811138681113868111386811138681113868111386811138681113888 1113889

2

11139741113972

(5)

AWSSG 1T

1113946T

0WSSGdt (6)

OSI 12

1 minus1113938

T

0 τrarrwdt11138681113868111386811138681113868

11138681113868111386811138681113868

1113938T

0 τrarrw

11138681113868111386811138681113868111386811138681113868dt

⎛⎝ ⎞⎠ (7)

RRT 1

(1 minus 2OSI) times AWSS (8)

where | τrarrw| is the magnitude of the instantaneous WSSvector τrarrw and T is the cardiac cycle

e numerical results are shown in Figures 11ndash15Focus of previous studies were mainly put on how EECPaffected the blood flow and pressure in diastole [1 12] Inthe current paper the velocity and pressure at time pointsof t 054T and t 058T were chosen to represent theblood velocity and pressure in diastole before and during

Velocity streamline (ms)

00

0375

075

1125

1 5

25

0 5

75

10(mm)

(a)

25

0 5

75

10(mm)

Velocity streamline (ms)

00

0375

075

1125

1 5

(b)

Figure 12 Blood velocity distributions in diastole (a) Pre-EECP t 054T (b) During EECP t 058T Note that EECP interventionsignificantly increased the blood velocity in diastole

Cardiology Research and Practice 7

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

EECP intervention respectively considering that peakblood velocity in diastole occurred at these time pointsbased on Figure 3

8 Discussions

e computational results are summarized in Table 2 whichinclude AWSS OSI and AWSSG over the cardiac cycle andbefore and during EECP intervention All calculations andstatistics were performed based on the whole model

e results showed that EECP performance signifi-cantly increased the blood velocity in diastole as well as theblood pressure Peak relative pressure during EECP in-creased about 2260 Pa comparing to pre-EECP state eelevation of diastolic pressure was thought playing a key

role for the increasement of perfusion [24] A calculationbased on Figures 3 and 4 showed that EECP performanceinduced a 126 elevation of the perfusion over a cardiaccycle in CCA

WSS has been widely recognized to be an importanthemodynamic factor affecting the initiation and develop-ment of atherosclerotic plaque It is now well accepted thatlow and oscillating WSS correlate positively with athero-sclerosis progression [25] Our calculating results showedthat EECP performance significantly increased theWSS levelin carotid bifurcation and especially in bulb and ICA andthe mean AWSS level throughout the model increased by169 (790 Pa versus 676 Pa)

As a factor proposed to represent the temporaryfluctuation of WSS OSI has been found to be associated

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(a)

AWSS (Pa)

0

5

10

15

20

25

0 5

75

10(mm)

(b)

Figure 13 AWSS distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS occurred at the internalcarotid artery (ICA) whereas low level AWSS occurred at bulb EECP intervention significantly increased the AWSS level at sinus of thebifurcation

8 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

with early atherosclerosis in some studies and region ofhigh OSI coincides with a high probability of occurrenceof early atherosclerosis lesions [26 27] Our resultsshowed that EECP performance didnrsquot induce a signifi-cant change in OSI level in the carotid artery althoughthis kind of intervention greatly changed the blood flowpattern

As a factor proposed to represent the spatial fluctuationof WSS WSSG has been suggested in some studies thatmight correlate with intima-medial thickness and endo-thelial dysfunction [27 28] Our current study showed thatEECP performance induced a significant increase in WSSGlevel in the carotid artery e mean and peak AWSSG levelthroughout the model respectively increased by 196

OSI

00

01

02

03

04

0

25

5

75

10(mm)

(a)

0

25

5

75

10(mm)

OSI

00

01

02

03

04

(b)

Figure 14 OSI distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level OSI occurred at bulb and EECPintervention didnrsquot induce significant change of OSI level

Cardiology Research and Practice 9

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

(201times 103 Pam versus 168times103 Pam) and 226(260times104 Pam versus 212times104 Pam)

One of the main limitations in the current study was thatwe did not enroll healthy subjects as comparison Becausethe aim of this paper was to introduce a medical imaging-based numerical method to assess the instant hemodynamicresponse during EECP treatment and to conduct a pilot

study of the influence of EECP on WSS and its fluctuationsin carotid bifurcation with mild plaque

9 Conclusions

We suggest that the framework of patient-specific numericalapproach developed in the current paper can be potentially

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(a)

AWSSG (times103Pam)

0

10

20

30

40

0

25

5

75

10(mm)

(b)

Figure 15 AWSSG distributions over the cardiac cycle (a) Pre-EECP (b) During EECP Note that high level AWSS mainly occurred atbifurcation site and ICA Meanwhile EECP intervention slightly increased the AWSSG level

Table 2 Hemodynamic statistics before and during EECP intervention for the whole model and over the cardiac cycle

AWSS (Pa) OSI AWSSG (Pam)Pre-EECP During EECP Pre-EECP During EECP Pre-EECP During EECP

Max 3869 4490 048 047 212times104 260times104

Min 073 070 32times10minus7 21times 10minus6 9311 9787Mean 676 790 0041 0042 168times103 201times 103

10 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

used in clinics for the assessment of instant hemodynamicresponse in the carotid artery during EECP treatment and inturn may play a role on improvement of the treatmentstrategies for better clinical outcome Meanwhile findings ofthis paper show that EECP treatment induced a significantaugmentation of blood perfusion and WSS level in thecarotid artery which may be the main hemodynamicmechanism underlying its good clinical effect for treatmentof the ischemic cerebrovascular diseases and the long-termeffect for inhibition of the atherosclerosis lesion

Data Availability

e data used to support the findings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conflicts of interest

Authorsrsquo Contributions

Jianhang Du and Guangyao Wu contributed equally to thiswork

Acknowledgments

is work was supported by the National Key RampD Programof the Ministry of Science and Technology of China (Grantno 2016YFC1301602) National Natural Science Foundationof China (Grant no 81661168015) and Shenzhen Scienceand Technology Innovation Commission (Grant nos JCYJ20160608153506088 YJ20180306174831458 and ZDSYS201703031711426)

References

[1] W Lin L Xiong J Han et al ldquoExternal counterpulsationaugments blood pressure and cerebral flow velocities in is-chemic stroke patients with cerebral intracranial large arteryocclusive diseaserdquo Stroke vol 43 no 11 pp 3007ndash3011 2012

[2] W E Lawson J C K Hui E D Kennard and G LinnemeierldquoEnhanced external counterpulsation is cost-effective in re-ducing hospital costs in refractory angina patientsrdquo ClinicalCardiology vol 38 no 6 pp 344ndash349 2015

[3] Task Force Members G Montalescot U Sechtem et al ldquo2013ESC guidelines on the management of stable coronary arterydiseaserdquo European Heart Journal vol 34 no 38 pp 2949ndash3003 2013

[4] E C Jauch J L Saver H P Adams et al ldquoGuidelines for theearly management of patients with acute ischemic strokerdquoStroke vol 44 no 3 pp 870ndash947 2013

[5] S D Fihn J C Blankenship K P Alexander et al ldquo2014ACCAHAAATSPCNASCAISTS focused update of theguideline for the diagnosis and management of patients withstable ischemic heart diseaserdquo e Journal of oracic andCardiovascular Surgery vol 149 no 3 pp e5ndashe23 2015

[6] A Raza K Steinberg J Tartaglia et al ldquoEnhanced externalcounterpulsation therapy past present and the futurerdquoCardiology in Review vol 25 no 2 p 59 2016

[7] J Du and L Wang ldquoEnhanced external counterpulsationtreatment may intervene the advanced atherosclerotic plaque

progression by inducing the variations of mechanical factorsa 3D FSI study based on in vivo animal experimentrdquo Mo-lecular amp Cellular Biomechanics vol 12 no 4 pp 249ndash2632015

[8] Y Zhang X He X Chen et al ldquoEnhanced external coun-terpulsation inhibits intimal hyperplasia by modifying shearstress-responsive gene expression in hypercholesterolemicpigsrdquo Circulation vol 116 no 5 pp 526ndash534 2007

[9] D P Casey C R Conti W W Nichols C Y ChoiM A Khuddus and R W Braith ldquoEffect of enhanced ex-ternal counterpulsation on inflammatory cytokines and ad-hesion molecules in patients with angina pectoris andangiographic coronary artery diseaserdquo e American Journalof Cardiology vol 101 no 3 pp 300ndash302 2008

[10] R W Braith C R Conti W W Nichols et al ldquoEnhancedexternal counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic anginardquo Circula-tion vol 122 no 16 pp 1612ndash1620 2010

[11] D-Y Yang and G-F Wu ldquoVasculoprotective properties ofenhanced external counterpulsation for coronary artery dis-ease beyond the hemodynamicsrdquo International Journal ofCardiology vol 166 no 1 pp 38ndash43 2013

[12] A D Michaels M Accad T A Ports and W GrossmanldquoLeft ventricular systolic unloading and augmentation ofintracoronary pressure and Doppler flow during enhancedexternal counterpulsationrdquo Circulation vol 106 no 10pp 1237ndash1242 2002

[13] A J Brown Z Teng P C Evans J H Gillard H Samady andM R Bennett ldquoRole of biomechanical forces in the naturalhistory of coronary atherosclerosisrdquo Nature Reviews Cardi-ology vol 13 no 4 pp 210ndash220 2016

[14] Y Mohamied E M Rowland E L Bailey S J SherwinM A Schwartz and P D Weinberg ldquoChange of direction inthe biomechanics of atherosclerosisrdquo Annals of BiomedicalEngineering vol 43 no 1 pp 16ndash25 2015

[15] X Li X Liu X Li L Xu X Chen and F Liang ldquoTortuosity ofthe superficial femoral artery and its influence on blood flowpatterns and risk of atherosclerosisrdquo Biomechanics andModeling in Mechanobiology vol 18 no 4 pp 883ndash896 2019

[16] L Xu F Liang B Zhao J Wan and H Liu ldquoInfluence ofaging-induced flow waveform variation on hemodynamics inaneurysms present at the internal carotid artery a compu-tational model-based studyrdquo Computers in Biology andMedicine vol 101 pp 51ndash60 2018

[17] R Gonzalez R Woods and S Eddins Digital Image Pro-cessing Using Matlab Publishing House of Electronics In-dustry Beijing China 2004

[18] P Rosin Y Lai C Liu et al ldquoVirtual recovery of content fromX-ray micro-tomography scans of damaged historic scrollsrdquoScientific Reports vol 8 no 1 Article ID 11901 2018

[19] C Liu and W Hu ldquoReal-time geometric fitting and poseestimation for surface of revolutionrdquo Pattern Recognitionvol 85 pp 90ndash108 2019

[20] R B Bird R C Armstrong and O Hassager Dynamics ofPolymeric Liquids Fluid Mechanics Wiley New York USA1987

[21] S Tian ldquoWall effects for spherical particle in confined shear-thickening fluidsrdquo Journal of Non-Newtonian Fluid Me-chanics vol 257 pp 13ndash21 2018

[22] F Rikhtegar J A Knight U Olgac et al ldquoChoosing theoptimal wall shear parameter for the prediction of plaquelocationmdasha patient-specific computational study in humanleft coronary arteriesrdquo Atherosclerosis vol 221 no 2pp 432ndash437 2012

Cardiology Research and Practice 11

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice

[23] C V Cunnane EM Cunnane andM TWalsh ldquoA review ofthe hemodynamic factors believed to contribute to vascularaccess dysfunctionrdquo Cardiovascular Engineering and Tech-nology vol 8 no 3 pp 280ndash294 2017

[24] H Mueller S M Ayres andW J Grace ldquoHemodynamic andmyocardial metabolic response to external counterpulsationin acute myocardial infarction in manrdquoe American Journalof Cardiology vol 31 no 1 p 149 1973

[25] D Tang R D Kamm C Zheng et al ldquoImage-based modelingfor better understanding and assessment of atheroscleroticplaque progression and vulnerability data modeling vali-dation uncertainty and predictionsrdquo Journal of Biomechanicsvol 47 no 4 pp 834ndash846 2014

[26] D N Ku C K D P Giddens and S Glagov ldquoPulsatile flowand atherosclerosis in the human carotid bifurcation Positivecorrelation between plaque location and low oscillating shearstressrdquo Arteriosclerosis An Official Journal of the AmericanHeart Association Inc vol 5 no 3 pp 293ndash302 1985

[27] J R Buchanan C Kleinstreuer G A Truskey and M LeildquoRelation between non-uniform hemodynamics and sites ofaltered permeability and lesion growth at the rabbit aorto-celiac junctionrdquo Atherosclerosis vol 143 no 1 pp 27ndash401999

[28] J Murphy and F Boyle ldquoPredicting neointimal hyperplasia instented arteries using time-dependant computational fluiddynamics a reviewrdquo Computers in Biology and Medicinevol 40 no 4 pp 408ndash418 2010

12 Cardiology Research and Practice