\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[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Does diabetic early kidney damage alter renal elasticity?: An ultrasound
based 2D Shear wave elastography study}



\author[1]{Nesrin Gündüz}%
\author[1]{Aysenur Buz}%
\author[2]{Adnan Kabaalioglu}%
\affil[1]{Istanbul Medeniyet University Faculty of Medicine}%
\affil[2]{Koc University}%


\vspace{-1em}



  
  \date{May 04, 2024}


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





\selectlanguage{english}
\begin{abstract}
Objectives: Kidney damage caused by type-II diabetes mellitus (DM-II)
can disturb renal elasticity. There is a paucity of data whether early
kidney damage causes kidney stiffening. This comparative study aimed to
assess kidney elasticity in patients with DM-II with or without moderate
albuminuria using ultrasound based 2D shear wave velocity (2D-SWV).
Methods: For this prospective single center study, a sample size of at
least 32 was computed. Overall 57 cases (40 DM-II subjects with no
chronic kidney disease and 17 age and sex matched healthy controls) were
included. The DM-II subjects comprised moderate albuminuria (n=22) and
no-albuminuria (n=18) subgroups. Bilateral renal parenchymal 2D-SWV
values were separately measured from upper, mid and lower portions.
Groups were compared with T test or Mann-Whitney-U test as appropriate.
Inter-reader agreement was assessed by intra-class correlation
coefficient (ICC). Results: The median age {[}55.5 (50-62) vs 55
(48.5-59.5) years, respectively, p=0.48{]} and gender rates {[}18 (45\%)
vs 10 (58.8\%) females, respectively, p= 0.34{]} did not differ between
DM-II and control groups. The average and individual portion 2D-SWV
values were also similar (p\textgreater{}0.05 for all). The average
2D-SWV values were also similar between the albuminuria vs
no-albuminuria subgroups. The interobserver agreement was good (ICC:
0.66, 95\% CI: 0.19-0.88, p=0.006). Conclusion: The kidney elasticity
does not seem to be disturbed in patients with diabetes and a preserved
eGFR with or without moderate albuminuria.%
\end{abstract}%



\sloppy


\textbf{INTRODUCTION}

Chronic kidney disease (CKD) is defined as sustained kidney damage or
decrease of estimated glomerular filtration rate (eGFR) to less than 60
ml/min per 1.73 m\selectlanguage{ngerman}² body surface area lasting for \selectlanguage{english}[?]3 months (1). Diabetes
mellitus (DM) is one of the most common causes of kidney damage and
dysfunction (2). DM-II causes endothelial dysfunction and increased
permeability to proteins (3). Moderate albuminuria, defined as urinary
albumin to creatinine ratio (uACR) between 30-300 mg/g, is one of the
most commonly used biomarker of early renal injury.

The most common noninvasive imaging tool for the assessment of renal
diseases is ultrasonography (US) with renal size, cortical echogenicity
and cortical thickness being used as markers of CKD (4, 5). Although
these conventional US markers are well correlated with eGFR and severity
of albuminuria, they can be recognized relatively late in the disease
course where advanced damage to kidneys has already occurred (6). It is
well recognized that histological changes in kidneys start before a
measurable decline in eGFR and conventional US findings have occurred
(3). Typical histological changes in type-II DM (DM-II) include
glomerular changes which are related to proteinuria (7). Interstitial
fibrosis occur in the later stages, and are associated with a decline in
GFR and progressive deterioration of tissue elasticity and increased
renal stiffness (3, 6). Hence combination of moderately increased uACR
with preserved eGFR can be considered as a surrogate marker of early
kidney damage in patients with DM-II.

The so called gold standard method to detect early glomerular changes is
biopsy (8) which is invasive and inappropriate for prospective serial
follow-up (9). Moreover, biopsy sensitivity remains problematic due to
potential sampling errors (8, 10). Hence, elastographic methods have
been increasingly investigated to assess kidney stiffness including
magnetic resonance imaging (11) and US (6, 9, 12, 13). Among US
shear-wave elastography methods, 2D shear-wave velocity (2D-SWV) has
emerged as a relatively novel method to assess tissue stiffness and has
been reported to provide comparable results as compared to transient
elastography point shear-wave elastography (14, 15). There is lack of
evidence showing disturbances in renal elasticity caused by early
diabetic renal damage. This study aims to compare the renal elasticity
DM-II patients with preserved eGFR and healthy controls using US 2D-SWV.

\textbf{METHODS}

This prospective-observational single center study was conducted in
accordance with the Declaration of Helsinki and Institutional Research
Ethics Committee approved our study design. Written informed consent was
obtained from all participants.

\textbf{Study design and participants}

Sample size calculation for mean SWV's based on a previous publication
revealed a total of 30 patients to be enrolled (at least 15 healthy and
15 healthy controls). However, since we pre-planned to stratify DM-II
patients in two groups, doubling of sample size of DM-II subjects was
considered appropriate. The study was performed in our tertiary
institution on a three consecutive months period. Overall 57 subjects
including 40 outpatients with DM-II and 17 age and sex matched healthy
controls were enrolled. DM-II patients were recruited from internal
medicine or nephrology outpatient clinics and control subjects were
asked to participate in the study by in-hospital advertisements.

Patients with DM-II were divided into two groups according to the
presence of moderately elevated uACR {[}Groups with (Alb+) and without
(Alb-) albuminuria{]}. During initial scanning of subjects with DM-II,
those with more than mild reduction in eGFR (i.e. less than
\textless{}60 ml/min/1.73 cm2), more than moderate proteinuria (urine
ACR \textgreater{}300 mg/g) or already being treated for proteinuria,
other confirmed diabetic organ complications, any systemic disease with
a potential of renal involvement, history or symptoms of cardiovascular
diseases, or common risk factors for vascular diseases (i.e.
hypertension, smoking, dyslipidemia) were disqualified from the study.
The uACR was measured from early morning urine samples, in at least 2
occasions of at least 3 months apart. The eGFR was calculated with 2009
CKD-EPI formula using serum creatinine value measured in at least 2
occasions of at least 3 months apart (16).

None of patients were not scheduled for elastography assessment by the
clinician but were imaged for research purposes. Moreover, a scanning
conventional kidney US was performed after initial recruitment and those
with abnormal findings (renal tumor, hydronephrosis, congenital anomaly,
signs of acquired renal disease) were excluded.

\textbf{US shear-wave elastography technique}

2D-SWV based US elastography was performed using Toshiba Aplio i800
(Canon Medical systems, Japan) ultrasound system with an ultra-wideband
convex transducer (i8CX1). The images were obtained while the patients
lying in the lateral decubitus position with breath-hold during data
acquisition. The sample box was placed in the renal cortex of the upper,
middle and lower portions of each kidney, respectively (Fig. 1). A fixed
region-of-interest (ROI) size was chosen for each measurement. The
2D-SWV was measured 4-6 times for each renal portions and the mean of
the measurements were recorded accordingly. The mean 2D-SWV values of
the whole right and left kidneys were also calculated by averaging the
values of three renal portions. A second radiologist repeated the right
kidney average 2D-SWV measurements in randomly selected 10 healthy
subjects on the same day.

\textbf{Statistical Analysis}

Statistical analysis was performed with SPSS 19.0 (IBM SPSS Inc.
Chicago, IL, USA). The normality of continuous variables were analysed
by Shapiro-Wilk test. Descriptive statistics were reported as mean with
standard deviation for continuous variables with normal distribution and
as median with 25th-75th percentiles for those without. Categorical
variables were reported as frequencies with percentages. Independent
two-group comparisons for continuous variables without normal
distribution, were tested using Mann-Whitney U test. For continuous
variables with a normal data distribution, unpaired T-test was used. The
proportions were compared between the groups using Pearson's Chi-square
test in case the assumptions were met. Otherwise, Fisher's exact test
was used. Due to biological relationship between aging and loss of renal
function, a logistic regression analysis model including age and 2D-SWV
of relevant portions (those with intergroup p\textless{}0.05) was
constructed in order to predict the presence of Alb+ status.
Significance level was accepted at p\textless{}0.05 for all statistical
analyses.

A subgroup of a previous study included elasticity assessment of
patients resembling our study population (17). Based on the mean SWV's
taken from that study, we performed an a priori sample size calculation
using the prespecified alpha level of 0.05 and a beta level of 0.20 and
an expected effect size of 0.20 (a relative \%20 less SWV in healthy
subjects as compared to diabetics). A total sample size of 28 was
computed, we aimed to exceed 14 patients to be enrolled in each group.
Moreover since it was planned to stratify the DM-II patients into two
groups, the sample size of DM-II group was doubled.

\textbf{RESULTS}

Overall 57 patients including 40 with DM-II and 17 age and sex matched
healthy controls were included in the study. The median age {[}55.5
(50-62) vs 55 (48.5-59.5) years, respectively, p=0.48{]} and gender
rates {[}18 (45\%) vs 10 (58.8\%) females, respectively, p= 0.34{]} did
not differ between the groups. Inter-rater reliability analysis revealed
good agreement for 2D-SWV (ICC 0.66, 95\% CI: 0.19-0.88, p=0.006).

Patients with DM-II were further divided into two subgroups according to
uACR. Twenty two (55\%) of DM-II cases had moderately increased uACR and
18 (45\%) had no albuminuria. The age {[}55.5 (49.5-63) vs 56 (51-60.25)
years, respectively, p=0.71{]} and gender rates {[}11 (50\%) vs 7
(38.9\%), females, respectively, p=0.48{]} were similar between Alb+ and
Alb- subgroups.

\textbf{Comparison of 2D-SWV between DM-II vs Healthy subjects}

The average 2D-SWV of right {[}1.89 (1.73-2.18) vs 1.99 (1.83-2.38) m/s,
respectively, p=0.18{]} or left {[}1.91 (1.66-2.13) vs 1.95 (1.58-2.1)
m/s, respectively, p=0.92{]} kidneys did not differ between the DM-II
group and healthy controls. Moreover, the 2D-SWV values of the
individual (upper, mid, and lower) portions were also similar between
both groups (p\textgreater{}0.05 for all) for both kidneys (Table 1).

\textbf{Comparison of 2D-SWV between Alb+ vs Alb- subgroups}

The average 2D-SWV of right {[}2 (1.75-2.28) vs 1.83 (1.71-2.06) m/s,
respectively, p=0.32{]} or left {[}1.99 (1.69-2.24) vs 1.76 (1.55-2.1),
respectively, p=0.13{]} kidneys did not differ between the Alb+ and Alb-
subgroups. Only the 2D-SWV values of the upper pole of right kidney
{[}2.02 (1.46-2.43) vs 1.83 (1.63-2.11) m/s, respectively, p=0.04{]} and
mid portion of left kidney {[}1.96 (1.64-2.23) vs 1.54 (1.35-2) m/s,
respectively, p=0.03{]} were significantly higher in Alb+ subgroup.
However, the 2D-SWV of the remaining portions of both kidneys did differ
between both subgroups (Table 2).

\textbf{Effect of gender on 2D-SWV}

All the 2D-SWV's of the individual portions and the average 2D-SWV's of
both kidneys were similar between males and females (p\textgreater{}0.05
for all).

\textbf{Effect of age on 2D-SWV}

A weak positive correlation between age and average 2D-SWV's of left
kidneys was found (correlation coefficient: 0.29, p=0.03). However no
correlation was present between age and average 2D-SWV's of right
kidneys (correlation coefficient: 0.054, p=0.69).

\textbf{Prediction of albuminuria}

Since 2D SWV's of right kidney upper pole and left kidney mid portion
appeared to significantly differ between mAlb+ and mAlb- subgroups and
age showed some correlation with SWV, logistic regression analysis was
performed. The first model included age and left mid portion SWV and did
not reveal a significant predictor of albuminuria status. The second
model included age and the right upper pole SWV, again with negative
results (Table 3).

\textbf{DISCUSSION}

The main finding of current study is that, a significant change in renal
cortical elasticity was not found between patients with DM-II versus
healthy subjects or in albuminuria versus no-albuminuria subgroups.

DM-II causes microstructural changes in renal parenchyma before a
significant drop in eGFR occurs (3). A moderately increased uACR
indicates presence of kidney damage and is associated with future risk
of progression to kidney dysfunction and cardiovascular complications
independent of eGFR (16). We recognize that histological changes can be
present in a number of subjects with DM-II before pathologic amount of
urinary albumin can be detected (3, 7). Hence, one may argue that biopsy
is required for definitive confirmation of typical diabetic changes in
glomeruli (8). However, biopsy is not performed routinely in all cases
with DM-II and mostly reserved for certain indications (9). In the
landmark study by Fioretto P et al, microalbuminuric DM-II patients with
normal eGFR underwent kidney biopsy for research purposes rather than
for a clinical indication (18). They found histopathological changes
(either typical glomerular or atypical tubulointerstitial and vascular
changes), in 70\% of DM-II subjects. That was the basis that a
moderately elevated uACR in the setting of preserved eGFR was used as
representative of early diabetic renal injury in the current study where
biopsy was not available. We have found that, the early diabetic
histologic changes in kidneys do not necessarily translate into
disturbed elasticity, as we have not observed a difference in SWV values
between albuminuria and no-albuminurai subjects.

Conventional kidney US findings alone are inadequate for early
recognition of kidney damage in most cases. Indeed the typical US
findings of CKD represent late changes (4-6), which are already
irreversible. Moreover the conventional US findings of CKD are not
specific for diabetic nephropathy and diverse etiologies share the
common imaging changes. Elastography, on the other hand, has emerged as
a tool for assessment of increased tissue stiffness caused by damages to
organs including liver, breast, thyroid, prostate and kidney. The
relatively novel US shear-wave elastography method was used to assess
kidney stiffness in our study. 2D-SWV measurement by this technique has
provided comparable results to previously described methods including
transient elastography and acoustic radiation force imaging in depicting
liver fibrosis (15). Although SWV values are positively correlated with
amount of fibrosis in liver diseases (19), it is negatively correlated
with CKD stages and eGFR (6, 12). The underlying mechanism of the
inverse relationship between stiffness and eGFR in patients with CKD
remains unclear. Altered renal perfusion has been proposed to affect
stiffness measurements and explain this paradox (20). The ARFI derived
SWV has been found to be higher in patients with DM-II versus healthy
controls in one study (21). Moreover others revealed increased SWV in
DM-II induced early kidney damage but no CKD (i.e. eGFR still more than
60 ml/min/1.73m2) versus diabetic CKD (i.e. eGFR already less than 60
ml/min/1.73m2) (17). Interestingly our results does not support these
findings. The whole kidney average SWV's were not found to be increased
neither in DM-II vs healthy controls nor in mAlb+ vs mAlb- subjects in
current study. The contradiction between both studies can be explained
by the differences in study populations. Goya et al (17) did not report
any exclusion criteria in terms of comorbidities that may interfere with
elasticity results (hypertension, systemic diseases, other diabetic
organ complications, risk factors for vascular diseases). On the other
hand our population comprised a very selective group that presence of a
confounder of elasticity would be very unlikely. Another factor that may
influence the results is the sonographic technique used for elasticity
assessment. We used 2D-SWV measurement, whereas others used the ARFI
method.

The left middle and right upper portions' elasticity seemed to be
selectively disturbed in mAlb+ cases at univariate comparison. One may
argue that this may be attributable to the potentially asynchronous
severity of changes in different portions of kidneys (8, 10). Indeed,
heterogeneous renal histopathologic changes may occur in albuminuric
patients with DM-II (22, 23). However, both renal portions SWV values
were not independent predictors of mAlb+ status when adjusted for age by
multivariate analysis. Hence focal impaired elasticity in mAlb+ group as
compared to mAlb- group can not be considered plausible.

The impairment of whole kidney elasticity probably requires more
profound histological changes due to diabetic nephropathy. Previous
studies have shown reduced global kidney SWV values along with decreased
eGFR values with or without severe proteinuria (6, 12, 19). However
these findings probably require more severe kidney damage beyond
glomerulosclerosis such as tubulointerstitial fibrosis and vascular
changes which are deemed irreversible. We believe early recognition of
disturbed kidney elasticity as a surrogate marker of early kidney damage
is not possible by 2D-SWV measurement at this stage. However due to
conflicting results when compared with the previous work using ARFI
technique, further controlled longitudinal studies in larger series with
biopsy and histopathology being used as reference standard are required
in this regard.

The reproducibility of 2D-SWV was good in the current study with an
interobserver agreement ICC value of 0.66, which is close to previous
reports.

The major strength of our work is that it is the first study to evaluate
the ability of novel 2D-SWV US elastography technique in revealing early
kidney damage in patients with DM-II. Furthermore, application of strict
inclusion criteria to eliminate the potential confounders of disturbed
elasticity and proteinuria is another strength of our work. The sample
size was also calculated a priori, and the number of patients included
are adequate to reveal a difference between the SWV values of the study
groups.

The main limitations in current study is the absence of
histopathological confirmation of kidney damage. We believe, a
combination of moderate albuminuria with preserved eGFR is a quite
pragmatic way to reveal the early diabetic kidney damage, where biopsy
is not available. Although very unlikely, absence of a non-diabetic
cause of moderately increased uACR cannot be guaranteed based on
exclusion of diseases by history and symptoms alone.

In conclusion, the kidney elasticity does not seem to be disturbed in
patients with diabetes and a preserved eGFR with or without moderate
albuminuria.

\textbf{CONFLICT OF INTEREST:} None.

\textbf{REFERENCES}

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO
2012 clinical practice guideline for the evaluation and management of
chronic kidney disease. Kidney Int Suppl. 2013; 3: 1-150.

Webster AC, Nagler EV, Morton RL et al. Chronic kidney disease. Lancet.
2017; 389: 1238-52.

Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy.
J Am Soc Nephrol 2005; 16 Suppl 1: S30--S33.

Yamashita SR, von Atzingen AC, Iared W et al. Value of renal cortical
thickness as a predictor of renal function impairment in chronic renal
disease patients. Radiol Bras 2005; 48: 12-16.

Beland MD, Walle NL, Machan JT et al. Renal cortical thickness measured
at ultrasound: is it better than renal length as an indicator of renal
function in chronic kidney disease? AJR Am J Roentgenol 2010; 195:
W146--149.

Lin HY, Lee YL, Lin KD et al. Association of Renal Elasticity and Renal
Function Progression in Patients with Chronic Kidney Disease Evaluated
by Real-Time Ultrasound Elastography. Sci Rep. 2017; 7: 43303.

White KE, Bilous RW. Type 2 diabetic patients with nephropathy show
structural-functional relationships that are similar to type 1 disease.
J Am Soc Nephrol. 2000; 11: 1667-73.

Walker PD, Cavallo T, Bonsib SM; Ad Hoc Committee on Renal Biopsy
Guidelines of the Renal Pathology Society. Practice guidelines for the
renal biopsy. Mod Pathol 2004; 17: 1555-1563.

Sigrist RMS, Liau J, Kaffas AE et al. Ultrasound Elastography: Review of
Techniques and Clinical Applications. Theranostics. 2017; 7: 1303-1329.

Cunningham A, Benediktsson H, Muruve DA et al. Trends in Biopsy-Based
Diagnosis of Kidney Disease: A Population Study. Can J Kidney Health
Dis. 2018; 5: 2054358118799690.

Li J, An C, Kang L et al. Recent advances in magnetic resonance imaging
assessment of renal fibrosis. Adv Chronic Kidney Dis 2017; 24: 150-153.

Guo LH, Xu HX, Fu HJ et al. Acoustic radiation force impulse imaging for
noninvasive evaluation of renal parenchyma elasticity: preliminary
findings. PLoS One. 2013; 8: e68925.

Singh H, Panta OB, Khanal U et al. Renal Cortical Elastography: Normal
Values and Variations. J Med Ultrasound. 2017; 25: 215-220.

Lee ES, Lee JB, Park HR, et al. Shear Wave Liver Elastography with a
Propagation Map: Diagnostic Performance and Inter-Observer Correlation
for Hepatic Fibrosis in Chronic Hepatitis. Ultrasound Med Biol. 2017;
43: 1355-1363

Ferraioli G, De Silvestri A, Lissandrin R et al. Evaluation of
Inter-System Variability in Liver Stiffness Measurements. Ultraschall
Med. 2019; 40: 64-75.

Levey AS, de Jong PE, Coresh J et al. The definition, classification,
and prognosis of chronic kidney disease: a KDIGO Controversies
Conference report. Kidney Int. 2011; 80: 17.

Goya C, Kilinc F, Hamidi C, et al. Acoustic radiation force impulse
imaging for evaluation of renal parenchyma elasticity in diabetic
nephropathy. AJR Am J Roentgenol. 2015;204:324-329.

Fioretto P, Mauer M, Brocco E, et al. Patterns of renal injury in NIDDM
patients with microalbuminuria. Diabetologia 1996; 39: 1569-1576.

Yang H, Sun Y, Tang Y et al. Shear-wave elastography of the liver in a
healthy pediatric population. J Clin Ultrasound. 2020; 48: 139\selectlanguage{english}-144.

Asano K, Ogata A, Tanaka K et al. l. Acoustic radiation force impulse
elastography of the kidneys: is shear wave velocity affected by tissue
fibrosis or renal blood flow? J Ultrasound Med 2014;33:793-801.

Bob F, Grosu I, Sporea I et al. Ultrasound-Based Shear Wave Elastography
in the Assessment of Patients with Diabetic Kidney Disease. Ultrasound
Med Biol. 2017; 43: 2159\selectlanguage{english}-216.

Ekinci EI, Jerums G, Skene A et al. Renal structure in normoalbuminuric
and albuminuric patients with type 2 diabetes and impaired renal
function. Diabetes Care. 2013; 36: 3620-6.

Fioretto P, Mauer M. Diabetic nephropathy: diabetic
nephropathy-challenges in pathologic classification. Nat Rev Nephrol.
2010; 6 :508-510.

\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/417748/articles/524739-does-diabetic-early-kidney-damage-alter-renal-elasticity-an-ultrasound-based-2d-shear-wave-elastography-study}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/417748/articles/524739-does-diabetic-early-kidney-damage-alter-renal-elasticity-an-ultrasound-based-2d-shear-wave-elastography-study}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/417748/articles/524739-does-diabetic-early-kidney-damage-alter-renal-elasticity-an-ultrasound-based-2d-shear-wave-elastography-study}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}

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

