\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Investigation of a novel method for improving hemodynamics of Fontan
circuit using an experimental model}



\author[1]{Suneet Bhansali}%
\author[1]{Tsusheel Kumar}%
\author[2]{Maya Crawford Crawford}%
\author[3]{Nikhil R. Katre}%
\affil[1]{NYU Langone Health}%
\affil[2]{Northeastern University Department of Biology}%
\affil[3]{Veol Medical Technologies Pvt Ltd Navi Mumbai India}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
\textbf{Background:} The study objective was to test underlying physical
laws behind a proposed novel device for failing Fontan and investigate
whether the device could be implemented theoretically to improve
hemodynamics in failing Fontan circulation. \textbf{Methods}: A 4-arm
setup was designed and fabricated to simulate an actual Fontan circuit
in the form of a junction of the superior and inferior vena cavae (SVC,
IVC) with the right and left pulmonary arteries (RPA, LPA). A provision
for placement of an oscillating ball along the RPA-LPA path to push
fluid away from SVC and IVC was created. The rate of ball oscillations
and initial pressure of fluid on SVC and IVC limbs were varied. The
pressure-drop times in the vena cavae limbs were measured at varying
ball oscillations and resistances in the RPA-LPA pathway. The test was
considered positive if increasing oscillations of the ball allowed for
quicker pressure drop in the SVC and IVC limbs indicating quicker
discharge of fluid through the RPA and LPA. 48 different experiments
were conducted to simulate different physical conditions and the results
were plotted and analyzed to draw a conclusion. \textbf{Results}: The
time required for pressure drop in the experiment without ball was the
least across all set of readings. This meant that placing an oscillating
ball along the RPA -LPA path created obstruction to flow rather than
enhance it. Increasing rate of ball oscillations increased degree of
obstruction to flow. \textbf{Conclusion}: The proposed interventional
method is unsuitable for improving hemodynamics in failing Fontan
circulation.%
\end{abstract}%



\sloppy


\textbf{Title:} Investigation of a novel method for improving
hemodynamics of Fontan circuit using an experimental model

\textbf{Authors:} T.K. Susheel Kumar,~MD\textsuperscript{1},~Suneet
Bhansali, MD\textsuperscript{2}, Maya T Crawford\textsuperscript{3},
Nikhil R Katre,~Mdes\textsuperscript{4}

\textbf{Affiliations:}

\textsuperscript{1}Department of Congenital Cardiothoracic Surgery, NYU
Langone Health, New York, USA,

\textsuperscript{2} Department of Pediatric Cardiology, NYU Langone
Health, New York, USA

\textsuperscript{3}Department of Biology, Northeastern University,
Boston, USA

\textsuperscript{4}Veol Medical Technologies Pvt. Ltd., Navi Mumbai,
India

\textbf{Corresponding author} :

TK Susheel Kumar, MD

Associate Professor, Department of Congenital Cardiothoracic Surgery,

NYU Langone Health,

New York, NY 10016

Email: tksusheel.kumar@nyulangone.org

Phone: 212-263-1370

Fax: 212-263-0437

\textbf{Key words} : Fontan, complications, device, hemodynamics,
oscillating ball

Accepted for oral presentation at \emph{16th International Conference on
Pediatric Mechanical Circulatory Support Systems \& Pediatric
Cardiopulmonary Perfusion} ~on May 14-15, 2020 (Meeting Cancelled due to
COVID-19 Pandemic).

IRB Approval, consent, and clinical trial registration are not
applicable for this study. No patient data was accessed for the
completion of this study and manuscript.

\textbf{Main document word count} : 1861

\textbf{Abstract Word Count:} 250

\textbf{Statement of financial support} : No institutional or private
financial support was received for this study.

\textbf{Conflict of interest} : No potential conflict exists for any of
the authors

\textbf{Summary of author contributions}

Dr.TK Susheel Kumar contributed to the concept, design, data analysis,
drafting of the article and critical revision of the article

Dr. Suneet Bhansali contributed to the concept, data analysis, drafting
of the article and critical revision of the article.

Maya Crawford contributed to the concept, data analysis, drafting of the
article and critical revision of the article.

Nikhil R. Katre contributed to the concept, design, data collection,
data analysis, statistics and drafting of the article.

\textbf{Abstract}

\textbf{Background:} The study objective was to test underlying physical
laws behind a proposed novel device for failing Fontan and investigate
whether the device could be implemented theoretically to improve
hemodynamics in failing Fontan circulation.

\textbf{Methods} : A 4-arm setup was designed and fabricated to simulate
an actual Fontan circuit in the form of a junction of the superior and
inferior vena cavae (SVC, IVC) with the right and left pulmonary
arteries (RPA, LPA). A provision for placement of an oscillating ball
along the RPA-LPA path to push fluid away from SVC and IVC was created.
The rate of ball oscillations and initial pressure of fluid on SVC and
IVC limbs were varied. The pressure-drop times in the vena cavae limbs
were measured at varying ball oscillations and resistances in the
RPA-LPA pathway. The test was considered positive if increasing
oscillations of the ball allowed for quicker pressure drop in the SVC
and IVC limbs indicating quicker discharge of fluid through the RPA and
LPA. 48 different experiments were conducted to simulate different
physical conditions and the results were plotted and analyzed to draw a
conclusion.

\textbf{Results} : The time required for pressure drop in the experiment
without ball was the least across all set of readings. This meant that
placing an oscillating ball along the RPA -LPA path created obstruction
to flow rather than enhance it. Increasing rate of ball oscillations
increased degree of obstruction to flow.

\textbf{Conclusion} : The proposed interventional method is unsuitable
for improving hemodynamics in failing Fontan circulation.

\textbf{Abbreviations}

RPA: right pulmonary artery

LPA: left pulmonary artery

RV: right ventricle

IVC: inferior vena cava

SVC: superior vena cava

\textbf{Introduction}

Approximately 50 years ago, Francis Fontan pioneered an operation for
tricuspid atresia that bears his name today.\textsuperscript{1} The
Fontan procedure refers to any operation that shunts the systemic venous
return to the pulmonary bed by bypassing the right ventricle (RV) or the
subpulmonary ventricle. It can be applied to a wide array of congenital
heart diseases such as tricuspid atresia, hypoplastic left heart
syndrome and unbalanced atrioventricular canal where there is a single
functional ventricle. Despite restoring normal oxygen levels in the
body, the operation creates a neoportal system where adequate cardiac
output can be generated only at the expense of increased systemic venous
congestion.\textsuperscript{2} Additionally, the loss of pulsatility and
chronic low-flow state of Fontan circulation induces pulmonary
vasoconstriction and raises the pulmonary vascular resistance. This
results in slow but relentless damage to the end organ systems,
especially the liver. Numerous designs of assist devices that have been
previously described provide a push to the venous blood entering the
lungs to mimic a normal RV.\textsuperscript{3-5} A novel interventional
approach in the form of an oscillating ball along the pulmonary artery
pathway to improve the hemodynamics in failing Fontan circuit is studied
herewith. The objective of the experimental study was to test the
hypothesis that placement of an oscillating ball along the pulmonary
artery pathway in an experimental Fontan model would increase the
forward flow of blood into the lungs and reduce the pressure in the
systemic veins.

\textbf{Materials and methods}

An experimental model to mimic the Fontan circuit was created. The crux
of the model was the creation of a junction between the branch pulmonary
arteries and the vena cavae. The approximate dimensions of relevant
blood vessels in an average adult Fontan patient such as superior vena
cava (SVC), inferior vena cava (IVC), right pulmonary artery (RPA) and
left pulmonary artery (LPA) were used as reference (see Table 1). A
4-arm setup to mimic these dimensions as far as practically possible was
designed and fabricated using acrylic pipes and a specially made
junction. Table 1 describes the dimensions of the vessels in the human
body and the dimensions provided in the simulated setup. There was some
limitation in mimicking the actual anatomical dimensions in the
simulated setup because we used standard available components in the
setup.

A mechanical arrangement was designed and fabricated to enable placement
of a ball inside the 4-arm setup along the RPA-LPA pathway. Furthermore,
a driving mechanism was also fabricated to mechanically oscillate the
ball along the LPA-RPA pathway. (Figure 1)(Video 1) The dimension of the
ball selected was 18 mm such that it could move easily along the RPA-LPA
pathway without completely occluding it and allow fluid to pass around
the ball. The reason for keeping some gap between the ball and the
pathway was to avoid total dependence of the movement of the blood and
hemodynamics only on the motion of the ball. In case the ball failed,
blood would be still able to flow around the ball thereby providing a
safety mechanism.

Two fluid inlet reservoirs, one each was attached to the top of the SVC
and IVC limbs (Figures 2 and 3). The reservoirs were made of sufficient
height so that a pressure head of fluid equivalent to the actual venous
pressure in the venous side of the Fontan circuit could be created by
filling fluid into the reservoirs. We used two different fluids in the
setup; one was water and another was a mixture of water and glycerine to
simulate the viscosity of blood. Typical pressures in the SVC and IVC
along with the corresponding height of fluid column in the fluid inlet
reservoirs are mentioned in Table 2. We conducted experiments at two
levels of venous pressure head equivalent to 20mmHg and 10mmHg pressure
to mimic a high and low venous pressure Fontan system.

Two fluid outlet reservoirs, one each was placed below the RPA and LPA
to collect the fluid coming out. Stopcocks were placed one each at the
end of RPA and LPA limbs to control the flow of the fluid out of RPA and
LPA. The purpose of the stopcocks was to simulate various levels of
resistance to flow as encountered in patients with failing Fontan
circuit. We conducted experiments with three levels of resistance; 30
degree opening of the stopcock indicating high resistance to flow, 60
degree indicating low resistance and 90 degree indicating no resistance
(free-flow) condition.

The oscillating ball was intended to act as a pump to increase the rate
of fluid output coming out from the RPA and LPA. We used three speeds of
oscillation; 40 strokes /min, 72 strokes/min and 100 strokes/min to test
the hypothesis. A condition without the ball was also tested as a
baseline. In order to simulate the viscosity of blood, a mixture
consisting of 52\% Glycerin and 48\% water by volume was
made.\textsuperscript{6} This blood analog was used as one of the fluids
in the setup.

\textbf{Experiments}

We conducted two sets of experiments with the 4-arm setup. Set A of
experiments involved allowing the fluid pressure in the inlet reservoirs
to drop from predetermined level to zero and measuring the time required
to achieve this pressure drop (Videos 2 and 3). A total of 48 different
experiments were conducted under set A for various conditions as shown
in Table 3. In general, shorter time required to achieve pressure drop
indicates better drainage of fluid through the RPA-LPA pathway.

Set B of experiments involved maintaining the fluid pressure in the
inlet reservoirs constant by replenishing the fluid continuously. The
time required for flow of 1 liter of fluid each out of LPA and RPA at
constant pressure was recorded. A total of 12 different experiments were
conducted under set B for conditions as shown in Table 4. In general,
less time required for flow of set volume of fluid (a total of 2 liters)
indicates better drainage of fluid through RPA-LPA pathway.

\textbf{Results}

The readings for the set A experiments are shown in Figure 4 and Figure
5. It was noted across all the experiments in set A, the time required
for achieving pressure drop was the least when no ball was present in
the setup (which is free flow condition).

The readings for the set B experiments are shown in Figure 6. In set B,
it was noticed that the time required for a flow of 2 liters of fluid at
a constant pressure through the setup was least when there was no ball
in the setup.

Inference

The hypothesis behind conducting these experiments was that placement of
an oscillating ball would decrease the venous congestion and increase
the flow through the lungs in patients with failing Fontan circuit. The
experiments have proved that an oscillating ball does not help in
clearing the congestion, on the contrary, it may act as a hindrance to
flow.

\textbf{Discussion}

In the early 1970s, Francis Fontan and Kreutzer independently used the
concept of the `dispensable RV' to design a new circulation that had not
previously been witnessed in evolution.\textsuperscript{1,7} The `Fontan
operation' as it popularly became known as launched the era of surgical
treatment of functionally univentricular hearts. The Fontan operation
itself has also undergone numerous modifications in the last few decades
with the extracardiac Fontan operation being the most widely used design
today.\textsuperscript{8} Although the Fontan operation can be performed
with very low mortality today, the morbidity associated with this unique
circulation has become an ever increasing
problem.\textsuperscript{9}Early on, Dr. Francis Fontan himself
predicted the significant attrition associated with the new operation
over time.\textsuperscript{10} The entire problem of the Fontan
operation is related to the lack of the final push to the venous blood
before it enters the lungs. The Fontan operation essentially creates a
neo portal system where adequate LV loading can happen only at the
expense of raised central venous pressure.\textsuperscript{2} Moreover,
in the absence of a sub-pulmonary pump any small changes in the
resistance of this neo-portal system can lead to significant alterations
in cardiac output. The bottle neck of the cardiac output is the
resistance offered by this neo-portal system rather than the pumping
mechanism of the heart itself although in the final stages this too may
be affected and worsens the Fontan circulation all the more. The term
`Fontan failure' is a loosely applied term with some authors using it
solely for exercise intolerance, while others reserve it for late stages
of overt failure such as ascites, protein losing enteropathy and plastic
bronchitis. Perfusion of the liver is particularly endangered following
Fontan operation. Decreased portal blood flow coupled with chronic
elevation in pulmonary capillary bed pressure ultimately results in
fibrosis progressing to cirrhosis in many patients with Fontan
circulation.\textsuperscript{11}

Traditional heart failure therapy may not be as effective as medications
that can lower the resistance of the Fontan neo portal
system.\textsuperscript{12} Percutaneous creation of fenestration is
also not very effective as an intervention for failing Fontan patients.
Achieving a good balance between cyanosis, decreased congestion and
improved cardiac output can be challenging.\textsuperscript{13} Fontan
failure can sometimes be a consequence of structural issues that may be
amenable to surgical correction. Conversion of the atriopulmonary
connection to cavopulmonary connection using lateral tunnel technique or
extracardiac type of Fontan procedure reduces not only the energy loss
but also the transcoronary pressure gradient by placement of the
coronary sinus on the pulmonary venous side of the
circulation.\textsuperscript{14} Heart transplantation can provide
effective therapy for end stage Fontan failure. However, outcomes of
heart transplantation for the failing Fontan patient are not as
favorable as for other congenital heart diseases.\textsuperscript{15}The
continued shortage of donor organs with an ever increasing population of
Fontan patients and suboptimal outcomes of heart transplantation have
propelled the need for an effective mechanical circulatory support
device not only as a bridge to transplantation but also as a destination
device. Many patients with failing Fontan physiology have preserved
systemic ventricular function and hence application of a systemic
ventricular assist device is unlikely to be effective. For such patients
a right sided subpulmonary ventricular assist device may afford a better
solution. A variety of novel Fontan specific devices have been proposed
each with its own limitations (Table 5).\textsuperscript{3-5} Our study
was an attempt towards the same end. The purpose of this study was to
test whether the idea of an oscillating ball would work in the Fontan
circuit. The mechanism seemed simple and theoretically attractive. The
device, if successful could be potentially implemented in most adult
Fontan patients as an oscillating ball placed in a stent in the branch
pulmonary arteries within the existing Fontan configuration.
Unfortunately, as our own studies in the lab proved, the results were
counter intuitive. Perhaps, testing the concept within a closed circuit
or using computational flow dynamics may have yielded different results.
We hope our findings are useful for other groups making similar attempts
to address the problem of Fontan failure.

\textbf{Conclusion} :

The proposed novel method for intervention is not a suitable option for
improving hemodynamics in failing Fontan circulation. Other intervention
modalities to improve hemodynamics remain to be explored.

\textbf{References:}

1. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax.
1971;26(3):240-8.

2. Gewillig M, Goldberg DJ. Failure of the fontan circulation. Heart
Fail Clin. 2014;10(1):105-16.

3. Rodefeld MD, Coats B, Fisher T, et al. Cavopulmonary assist for the
univentricular Fontan circulation: von Karman viscous impeller pump. J
Thorac Cardiovasc Surg. 2010;140(3):529-36.

4. Lacour-Gayet FG, Lanning CJ, Stoica S, et al. An artificial right
ventricle for failing fontan: in vitro and computational study. Ann
Thorac Surg. 2009;88(1):170-6.

5. Pekkan K, Aka IB, Tutsak E, et al. In vitro validation of a
self-driving aortic-turbine venous-assist device for Fontan patients. J
Thorac Cardiovasc Surg. 2018;156(1):292-301 e7.

6. Chung J, Lee JJ, Choi J, Kim J, Min BG. Hydrodynamic and static
performance evaluation of the moving-actuator type biventricular assist
device, AnyHeart. ASAIO J. 2003;49(5):599-603.

7. Kreutzer G, Galindez E, Bono H, De Palma C, Laura JP. An operation
for the correction of tricuspid atresia. J Thorac Cardiovasc Surg.
1973;66(4):613-21.

8. Giannico S, Hammad F, Amodeo A, et al. Clinical outcome of 193
extracardiac Fontan patients: the first 15 years. J Am Coll Cardiol.
2006;47(10):2065-73.

9. Tokunaga S, Kado H, Imoto Y, et al. Total cavopulmonary connection
with an extracardiac conduit: experience with 100 patients. Ann Thorac
Surg. 2002;73(1):76-80.

10. Fontan F, Kirklin JW, Fernandez G, et al. Outcome after a
''perfect'' Fontan operation. Circulation. 1990;81(5):1520-36.

11. Wu FM, Ukomadu C, Odze RD, Valente AM, Mayer JE, Jr., Earing MG.
Liver disease in the patient with Fontan circulation. Congenit Heart
Dis. 2011;6(3):190-201.

12. Ghanayem NS, Berger S, Tweddell JS. Medical management of the
failing Fontan. Pediatr Cardiol. 2007;28(6):465-71.

13. Rupp S, Schieke C, Kerst G, et al. Creation of a transcatheter
fenestration in children with failure of Fontan circulation: Focus on
extracardiac conduit connection. Catheter Cardiovasc Interv.
2015;86(7):1189-94.

14. Huddleston CB. The failing Fontan: options for surgical therapy.
Pediatr Cardiol. 2007;28(6):472-6.

15. Backer CL, Russell HM, Pahl E, et al. Heart transplantation for the
failing Fontan. Ann Thorac Surg. 2013;96(4):1413-9.

\textbf{Tables}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Table
1. Dimensions of various components of mechanical set up. Anatomical
values refer to average dimensions in an average sized Fontan patient.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Table 2. Pressure and level of fluid used in experimental set up

Table 3. Set A (pressure drop) experiments\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Table 4. Set B (constant pressure) experiments

Table 5. Other attempts at cavopulmonary assist devices\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Author\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Concept\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Challenges\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Rodefeld et al (Reference 3)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Viscous impeller pump based on the Von Karman viscous pump
principle\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Design of expandable impeller Need for reduced scale in children Risk of
hemolysis Risk of thrombosis\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Lacour-Gayet et al (Reference 4)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Low pressure axial flow pump (`artificial RV') powered by electricity to
produce a continuous low suction inflow pressure on the venous
side\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Requires reconfiguration of existing Fontan circuit Requires open heart
surgery for implantation Risk of hemolysis Risk of thrombosis\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Pekkan et al (Reference 5)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Implantable integrated aortic turbine venous assist system based on
transfer of energy from single ventricle outlet to the venous side to
reduce the venous pressure\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Need for reduced scale in children Risk of turbine flow pathway blockage
Risk of hemolysis Risk of thrombosis\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}



\textbf{Figure legends}

Figure 1. Schematic diagram of the Fontan experimental set up.

Figure 2. Photo of the actual set up.

Figure 3. Computer model of actual set up.

Figure 4 showing set A pressure drop experiments with water.

Figure 5 showing set A pressure drop experiments with mixture of
Glycerin and water (blood analog)

Figure 6 showing set B constant pressure experiments with mixture of
Glycerin and water.

\textbf{Video legends (Supporting Information)}

Video 1. Working of the 4-arm setup

Video 2. Set A experiment with 140mm water column, no resistance, ball
oscillations at 40pm and experiment with 140mm Water column, no
resistance, no ball oscillations.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-6/Figure-6}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

