超声弹性技术评价旁观颈

d Original ContributionQUANTITATIVE ASSESSMENT OF BLADDER NECK COMPLIANCE BY USING TRANSV AGINAL REAL-TIME ELASTOGRAPHY OF WOMENH UANG Y ING,*L IU D A,y J IANG L UO,*L IU L I-X IA,*X IA Y U,*X IE L I-M EI,*and R EN W EI-D ONG**Department of Ultrasound,Shengjing Hospital of China Medical University,Shenyang,China;and y Department of Orthopaedic Surgery,Shengjing Hospital of China Medical University,11Shenyang,China(Received14November2012;revised18April2013;infinal form22April2013)Abstract—To assess the feasibility of using ultrasound real-time elastography(RTE)to measure bladder neck compliance,we performed real-time elastography measurements by manually applying repetitive compression with the transducer on the scan position of the bladder neck.Instant elastography index(EI)and mean EI of anterior and posterior lips of the bladder neck were calculated.The EI values of anterior and posterior lips of the bladder neck were analyzed in relation to age,body surface area,body mass index,detrusor wall thickness and length,width and thickness of the bladder neck in healthy women.The intra-observer and inter-observer repeatability of measurements in different parts of the bladder neck were assessed using intra-class correlation coefficients with95%confidence intervals and Bland–Altman analysis.There were no statistically significant differences between elastography measurements made by the same or two different observers in each area measured.There was no significant difference between anterior and posterior lip thickness of the bladder neck.The distribution of the elastography measurements indicated that the anterior lip of the bladder neck was slightly harder than the posterior lip.On the whole,from the results of the study,it was clear that EIs of the bladder neck were related to age in healthy women.Stepwise multiple regression analysis results revealed that age was the only independent factor modulating compliance of the bladder neck in healthy women.It is possible to provide a reproducible semi-quantification of real-time elastography in bladder neck compliance.(E-mail: spinecmu@)Ó2013World Federation for Ultrasound in Medicine&Biology.Key Words:Bladder neck,Elastography,Transvaginal ultrasound.INTRODUCTIONConditions causing bladder-outlet obstruction(BOO)in women include,but are not limited to,scarring of the bladder neck,advanced pelvic organ prolapse,neurologic conditions that cause detrusor sphincter dyssynergia, primary bladder neck obstruction(PBNO),urethral stric-ture disease,pelvicfloor muscle hyperactivity and dysfunctional voiding.PBNO is a significant source of pain and inconvenience to the patient.In PBNO,the bladder neck fails to open adequately during voiding,ob-structing the urinaryflow in the absence of other anatomic obstruction or increased striated sphincter activity.The precise etiology of PBNO remains to be defined,but several potential factors have been proposed, including muscular and neurologic dysfunctions and fibrosis(Padmanabhan and Nitti2007).Evaluation of BOO in women has proven a particular challenge.To date,most investigations have been based on pressure-flow tests(Dietz and Haylen2005),which are invasive,expensive and time consuming.Advances in ultrasonic technologies to measure bladder wall thick-ness(BWT)(Bright et al.2010;Kuhn et al.2010)and detrusor wall thickness(DWT)(Kessler et al.2006; Lekskulchai and Dietz2008)and estimate bladder weight(Chalana et al.2005)of urinary bladders are promising for quantifying bladder wall hypertrophy.It has been hypothesized that such measurements of bladder neck compliance may have important implications for clinical diagnosis and treatment of PBNO in females.Real-time elastography(RTE)is a recently devel-oped technique that allows non-invasive estimation of the elastic properties of in vivo tissue.This technique is based on the fact that soft tissue deforms more easily than hard tissue.The difference in deformation translates into a difference in ultrasound signals,which can be visu-ally represented by a color map.Moreover,the hardness of a target tissue can be semi-quantitatively estimatedAddress correspondence to:Liu Da,Department of Orthopaedic Surgery,Shengjing Hospital of China Medical University,Sanhao Street,Shenyang110004,China.E-mail:spinecmu@1727Ultrasound in Med.&Biol.,Vol.39,No.10,pp.1727–1734,2013 CopyrightÓ2013World Federation for Ultrasound in Medicine&BiologyPrinted in the USA.All rights reserved0301-5629/$-see front matter/10.1016/j.ultrasmedbio.2013.04.015by comparing its strain rate with that of a reference body (known as the strain ratio).Therefore,this study was designed to determine an objective elastography semi-quantitative strategy for bladder neck compliance in women.METHODSStudy populationFemale volunteers were randomly sampled from the outpatient population treated in the Department of Ultra-sound,Shengjing Hospital of China Medical University (Shenyang,China).None of the volunteers had received prior pharmacologic treatment,experienced spontaneous improvement of urinary tract symptoms or underwent previous operations of the urinary tract.In addition,none of the volunteers had a small pelvis,neurologic deficit or diabetes mellitus.A diagnosis of urethral caruncle,urethral stricture,urinary mucosa prolapse or urethral tumor was an indication for study exclusion.The study was conducted with approval from the local institutional review board and informed consent state-ments submitted by each participant in our study.The volunteers were asked to empty their bladders,and those with a post-void residual urine volume .50mL were excluded from further analysis.Post-void residual urine volume was measured by transabdominal ultrasound (US),in which one dimension in the trans-verse plane and two dimensions in the mid-sagittal plane were measured,then multiplied together,and finally multiplied by 0.7(Huang et al.2012).Ultimately,174women met all the inclusion criteria and were asked tojoin the study,and 115agreed to participate.Age,height and weight were recorded for each study participant,and body surface area (BSA)and body mass index (BMI)were calculated.Ultrasound measuresFor imaging analysis,the women were placed in the dorsal lithotomy position to facilitate scanning with an ultrasound machine (LOGIQ 9,GE Healthcare,Zipf,Austria)equipped with a 5-to 9-MHz transvaginal probe and ElastoScan elastography software.The transducer was positioned in the vagina and tilted upward to visu-alize the bladder neck in the mid-sagittal (Fig.1)and transverse sections.The position of the bladder neck is determined relative to the inferoposterior margin of the symphysis pubis (Dietz 2010;Hung et al.2011;Tunn and Petri 2003).Length of the bladder neck is the greatest dimension from the internal urethral orifice to the level of the inferior border of the symphysis pubis in the mid-sagittal plan,that is,point A to point B.Width of the bladder neck is the greatest dimension perpendic-ular to the first plane in the transverse plan.Anterior and posterior lip thickness (the greatest dimension from the urinary mucosa to the margin of the bladder neck perpendicular to the first plane in the mid-sagittal plan)of the bladder neck was measured too (Fig.1).Detrusor wall thickness was defined as the ratio of the thickness of the iso-echogenic layer to that of the hypo-echogenic layer at the bladder dome opposite the internal urethral meatus of the mid-sagittal plane (Fig.1).Three separate measurements were made,and the mean was calculated (Dietz 2004).Fig.1.Imaging the bladder neck of a 35-y-old woman.(a)Schematic representation of imaging of the bladder neck in the mid-sagittal plane.The bladder neck is supported well above the level of the inferior border of the symphysis pubis.The dotted line (L1)indicates the inferior margin of the symphysis pubis,that is,the reference for measurement of bladder neck position.The dotted line (L2)indicates the position for measurements of anterior and posterior lip thickness of the bladder neck.(b)Gray-scale ultrasound image of the bladder neck in the mid-sagittal plane.Detrusor wall thickness was defined as the thickness of the iso-echogenic layer to that of the hypo-echogenic layer at the bladder dome oppositethe internal urethral meatus of the mid-sagittal plane.1728Ultrasound in Medicine and Biology V olume 39,Number 10,2013After switching to the elastography pattern,the RTE image was obtained by manually applying slight repeti-tive compression (rhythmical compression/relaxation cycle)with the transducer in the mid-sagittal scanning plane.Patients were asked to remain absolutely still,as movement or coughing can interfere with the scan so that an image cannot be obtained.A region of interest was selected to cover the whole bladder neck in width and depth,and the elasticity information was presented on a color map,with blue indicating harder tissue and red indicating deformable,soft tissue.When the indicator of compression velocity on the lateral part of the RTE image was green and the waveform had a regular curve,the velocity of compression was adequate to calculate local strains.The US images were saved in digital format and stored on a hard disk for subsequent review and anal-ysis.We selected two regions of interest in the bladder neck for detailed analysis:the anterior lip of the bladder neck (A)and the posterior lip of the bladder neck (B).A circle,about 5mm in diameter,was placed in each of the two regions equidistant from the tip of the transducer;theUS machine automatically displayed an instant elastogra-phy index (EI)value for each circle (Fig.2).E1and E2indicate the instant EI values of regions A and B,respec-tively.E2/E1is the ratio of EI values.Afterward,the mean EI of each region during the elastrography process was displayed by the Q-analysis ElastoScan elastography software (Fig.3).Bladder neck elastography was carried out in tripli-cate by a single operator to eliminate the risk of intra-observer bias in the analysis.However,in 30recurrent cases,a second operator performed the bladder neck elastography,and this measurement was compared with the first measurement made by the previous operator to estimate inter-observer reproducibility.The mean value of triplicate measurements was used for statistical analysis.Statistical analysisThe intra-observer and inter-observer repeatability of measurements was assessed using intra-class correla-tion coefficients with 95%confidence intervals(CIs).Fig.2.Instant elastrographic images of the bladder neck of (a)a 35-y-old woman and (b)a 61-y-old woman.Left:Gray-scale ultrasound image of the bladder neck.Right:Elastogram indicating the regions of interest selected in the bladderneck.Region A:Anterior lip of the bladder neck.Region B:Posterior lip of the bladder neck.Bladder neck compliance assessment using RTE d H.Y ING et al .1729The difference in observational variability was analyzed according to the technique of Bland and Altman (1986).Associations between the bladder neck compliance parameters and age,BSA,BMI,detrusor wall thickness,length,width and thickness of the bladder neck were also assessed with Spearman’s correlation coefficients.Step-wise multiple regression analysis was performed to assess linear associations between EI values of the anterior and posterior lips of the bladder neck (as the dependent vari-ables)and determinants of clinical parameters (including age,BSA,BMI,detrusor wall thickness,length,width and thickness of the bladder neck).Differences in means of the continuous variables were evaluated with Student’s t -test.A p -value #0.05was considered to indicate statistical significance.The Statistical Package for Social Sciences (SPSS)software,Version 17.0,was used for all statistical analyses.RESULTSDemographic characteristics and measured parame-ters of the study participants are listed in Table 1.In general,sonography revealed that the bladder neck had a clear border and smooth surface.The anterior and posterior lips of the bladder neck were hypo-echoic (Fig.1).There was no significant difference in thickness between the anterior and posterior lips (0.5160.12vs.0.5460.12,p 50.385).In bladder neck elastography of the women,the green-blue signals of the bladder neck were surrounded by the intermediate red-yellow signals of soft tissue (Fig.2).Afterward,the mean EI of each region imaged in the elastography process was displayed using Q-analysis ElastoScan elastography software (Fig.3).The distribution of elastography measurements indicated that the anterior lip of the bladder neck was slightly harder than the posterior lip (1.9761.08vs.1.3260.72,p ,0.05).For the entire study population,a positive correla-tion was observed between the EI of the anterior lip of the bladder neck and age (r 50.393,p ,0.05)and the EI of the posterior lip of the bladder neck (r 50.632,p ,0.01).A positive correlation was also found between the EI of the posterior lip of the bladder neck and age (r 50.358,p ,0.01),length (r 50.369,p ,0.05)Fig.3.Quantification of the bladder neck compliance of (a)a 35-y-old woman and (b)a 61-y-old woman.The mean elastography index (EI)of each region during elastography was displayed using Q-analysis ElastoScan elastography soft-ware.Curve A:Anterior lip of the bladder neck.Curve B:Posterior lip of the bladder neck.1730Ultrasound in Medicine and Biology V olume 39,Number 10,2013and width (r 50.498,p ,0.01)of the bladder neck.The EI of the bladder neck was not significantly associated with BSA (r 50.009,p 50.86),BMI (r 50.002,p 50.97)or detrusor wall thickness (r 50.002,p 50.432).Figure 4is the plot of the elastographic index of thebladder neck versus age.In general,from the results of the study,it was clear that the EI of the bladder neck was age related.Stepwise multiple regression analysis revealed that age (p ,0.05)was the only independent factor modu-lating compliance of the bladder neck.The EI of the ante-rior lip of the bladder neck was independently influenced by age (p ,0.05).The EI of the posterior lip of the bladder neck was independently influenced by both age (p ,0.05)and width of the bladder neck (p ,0.01)(Table 2).BSA,BMI and detrusor wall thickness did not significantly influence the EI in this group of patients.The intra-class correlation coefficients for intra-observer and inter-observer reproducibility of the various elastography measurements are summarized in Table 3.Intra-observer and inter-observer intra-class correlation coefficients were statistically significant in each area measured.The data indicating the degree of concordance between pairs of measurements made by the same observer and by two different observers are summarized in Table 4.In all cases,there was no significant bias (p .0.05)because the difference between measurementsTable 1.Demographic characteristics of the studysubjects (115female volunteers)*Clinical parameters Age (years)3568.98(26–65)Height (cm)164.265.1Weight (kg)60.468.2Body surface area (m 2) 1.7560.4Body mass index (kg/m 2)25.562.1Detrusor wall thickness (mm)3.161.56Ultrasound parameters of bladder neck Length (mm) 2.1060.32Width (mm)1.2560.20Anterior lip thickness (mm)0.5160.12Posterior lip thickness 0.5460.12Elastography index (EI)Anterior lip 1.9761.08Posterior lip1.32672*Continuous variables are expressed as means 6standarddeviations.Fig.4.Plots of the elastographic index of (a)the anterior lip and (b)the posterior lip of the bladder neck versus age.Bladder neck compliance assessment using RTE d H.Y ING et al .1731remained stable and the mean and standard deviation of differences appeared constant throughout the range of measurements for all comparisons.DISCUSSIONOver the past several years,BOO in women has become an increasingly recognized entity(Lemack 2006).The type of obstruction may be divided broadly into functional and anatomic,including inflammatory processes of the bladder neck,fibrosis,urethral stricture, pelvic prolapse,neoplastic compression,iatrogenic obstruction and functional obstruction(Patel and Nitti 2001).Although a urodynamic study is considered to be the best diagnostic tool for assessing lower urinary tract function,some studies have clearly found a lack of corre-lation between symptoms and urodynamic diagnoses.In addition,it is generally believed that X-rays and cystos-copy examinations are not routinely warranted because of their radiation source and invasive nature,respectively (Coblentz et al.2001).Bladder wall hypertrophy has been documented in men with BOO(Oelke et al.2007),women with detrusor overactivity(Kuo2009)and children with urethral valves,dysfunctional voiding or neurogenic bladder dysfunction(Tanaka et al.2008).In addition,determina-tion of post-void residual urine volume is an attractive surrogate for BOO,as it can be measured non-invasively with bladder US(Al-Shahrani and Lovatsis 2005).The recently developed RTE has many benefits over the previously available procedures(Molina et al.2012). Elastography reveals the relative stiffness of different parts of tissues,rather than providing an objective measurement of stiffness(Berzigotti et al.2010).In contrast to the study of tumors,where the stiffness is compared with that of normal adjacent tissues equidistant from the tip of the transducer,the application of elastog-raphy in the study of the bladder neck is limited by the lack of a reference tissue for comparison.Unlike differen-tiating a malignant tumor by comparing it with the adja-cent benign tissue,the results were obtained as a relative variation in the stiffness of the anterior and posterior lips of the bladder neck.Elastography has been successfully used in the assessment of tumors in various organs,including the prostate(Kapoor et al.2011),breast(Gong et al.2011; Thomas et al.2010),thyroid gland(Ding et al.2011), salivary gland tissue(Bhatia et al.2010)and liver (Inoue et al.2010),because malignant tumors have been shown to be stiffer than benign ones.Elastography is also being evaluated for its efficacy as a tool for imaging the uterinefibroids in more detail than is currently possible with B-mode imaging(Ami et al. 2009).In addition,elastography of the uterine cervix during pregnancy and labor has been reported(Molina et al.2012;Swiatkowska-Freund and Preis2011). Recently,transvaginal sonography was used to study bladderfilling and bladder wall thickness and was confirmed as helpful in assessing bladder wall disease (Panayi et al.2010).In the present study,transvaginal sonography was selected because of its superior capa-bility in imaging the bladder neck and its insensitivity to interference by fat content(obesity),bowel gas or filling degree of the bladder,compared with transabdomi-nal sonography.Determination of residual urine volume may help in the clinical diagnosis of bladder neck obstruction; however,because residual urine can be caused by many different factors,including feeble detrusor(Oelke et al. 2007;Patel and Nitti2001),we measured the EI of the bladder neck when the post-void residual urine volumeTable2.Multiple regression analysis of the whole studygroup(N5115)Parameter RegressioncoefficientStandarderror T pEI of anterior lip*Age(years)0.0470.02 2.4170.022EI of posterior lip yAge(years)0.0290.013 2.1680.038Width of bladder neck(mm) 2.6220.807 3.2470.003EI5elastography index.*Model:R250.128,F55.84,model probability,0.05.y Model:R250.224,F510.546,model probability,0.01.Table3.Intraclass correlation coefficients of EI in different bladder neck areasMeasurement Intraclass coefficient95%confidence interval Standard deviation ofdifferences pEI of anterior lipSame observer0.780.71–0.860.07,0.05 Two observers0.720.65–0.780.12,0.05 EI of posterior lipSame observer0.830.78–0.870.13,0.05 Two observers0.730.68–0.800.19,0.05 EI5elastography index.1732Ultrasound in Medicine and Biology V olume39,Number10,2013of volunteers was,50mL.In this condition,the wall of the bladder neck was relaxed and not thickened,so that the measurements obtained were expected to not be subject to interference by the associated tension of the bladder neck with increased urine volume.Thus,we did not consider residual urine a parameter in our study. The EI of the bladder neck was not significantly associ-ated with detrusor wall thickness in healthy women in our study,but we think there are some correlations among residual urine,detrusor wall thickness and EI of the bladder neck in symptomatic women,and we plan to do more research in symptomatic women.Our study has confirmed that there was a lack of homogeneity in the measurable stiffness of theanterior and posterior lips of the bladder neck.We considered that thisfinding may indicate that the posterior lip of the bladder neck was subjected to a greater degree of pressure by the transducer than the anterior part,which is located further away from the probe.In our study,stepwise multiple regression analysis revealed that age was the only independent factor modu-lating compliance of the bladder neck.We think there are some correlations between the EI andfibrosis of the bladder neck in healthy women with increasing age.As a result,the bladder neck fails to open adequately during voiding,obstructing the urinaryflow in the absence of other anatomic obstruction.Collectively,thefindings of this study indicate that it is possible to provide an objective semi-quantification of elastrographic colors for the bladder neck.In this study, only generally healthy women without lower urinary tract symptoms were selected for analysis.But quantification of bladder neck compliance for the assessment of urinary tract diseases,prediction of treatment outcomes and longitudinal studies investigating disease development and progression should to be further evaluated after a series of studies in symptomatic women.Thus,the EI of the bladder neck might be suitable for future routine use in patients to help assess BOO in women through a non-invasive approach.Finally,this study found that RTE measurement of the bladder neck is an accurate method with which to assess compliance of the bladder neck.CONCLUSIONSThis study indicates that real-time elastography measurements of the bladder neck are possible and constitute an objective semi-quantitative strategy to assess compliance of the bladder neck in women. 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