Bladder Wall Thickness on Ultrasonographic Cystourethrography

Article Bladder Wall Thickness on Ultrasonographic Cystourethrography Affecting Factors and Their Implications Jenn-Ming Yang, MD, Wen-Chen Huang, MD Objective. To explore factors affecting bladder wall thickness on ultrasonographic cystourethrography in female patients with lower urinary tract symptoms. Methods. The records of 492 female patients with lower urinary tract symptoms who had undergone a urodynamic study and ultrasonography of the lower urinary tract and who had normal urinalysis findings, negative urine culture results, or both were identified from our urogynecologic database. These included 248 patients with urodynamic stress incontinence, 38 with detrusor overactivity, 39 with mixed incontinence, 35 with a hypersensitive bladder, 42 with voiding difficulty, and 90 with normal urodynamic findings. Results. Age, resting bladder neck angle, urethral mobility, and maximum urethral closure pressure were significantly associated with bladder wall thickness at the trigone and dome. Bladder wall thickness at the trigone was correlated with that at the dome (P <.0001). Bladder wall thickness at the trigone was positively correlated with pressure transmission ratios in the first and second quarters of the urethra (P <.0001; P =.002, respectively), whereas that at the dome was positively correlated with intravesical pressure at maximum flow and with detrusor opening pressure (P =.027; P =.046, respectively). Age and intravesical pressure at maximum flow were independently associated with bladder wall thickness at the trigone and dome (P =.007; P =.028), respectively. A thickened bladder wall was a common finding in female lower urinary tract symptoms, except in the patients with a hypersensitive bladder. Conclusions. Demographic, anatomic, and urodynamic factors may affect the bladder wall thickness at the trigone, dome, or both. Key words: bladder wall thickness; lower urinary tract symptoms; urodynamics. Abbreviations LUTS, lower urinary tract symptoms Received January 16, 2003, from the Division of Urogynecology, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China (J.-M.Y.); and Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan, Republic of China (W.-C.H.). Revision requested February 25, 2003. Revised manuscript accepted for publication March 4, 2003. Address correspondence and reprint requests to Jenn-Ming Yang, MD, Division of Urogynecology, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92 Chung-Shan N Rd, Section 2, Taipei 104, Taiwan, Republic of China. E-mail: yangjm0211@hotmail.com. Ultrasonography has recently replaced other radiologic methods in the anatomic evaluation of urinary incotinence 1,2 and has been used to explore the morphologic implications of female lower urinary tract symptoms (LUTS). 3,4 Khullar et al 3 reported that an increase in mean bladder wall thickness is unique to detrusor overactivity. With a cutoff value of 5 mm, bladder wall thickness had sensitivity of 84% and specificity of 89% for detecting detrusor overactivity. 3 Khullar et al 3 speculated that the increased bladder wall thickness in this disorder is secondary to detrusor hypertrophy associated with increased isometric detrusor contraction, urethral sphincter volume, and urethral closure pressure. A cystocele causing urethral obstruction has also been cited as a cause of a thickened bladder wall. Our findings from a previous study, 4 however, were different. In an investigation of the morphologic features of 2003 by the American Institute of Ultrasound in Medicine J Ultrasound Med 22:777 782, 2003 0278-4297/03/$3.50

Bladder Wall Thickness on Ultrasonographic Cystourethrography 1049 female patients with a single urodynamic diagnosis of urodynamic stress incontinence, detrusor overactivity, or hypersensitive bladder, increased mean bladder wall thickness was present in the first 2 conditions but not in the hypersensitive bladder. Age, parity, menopause, bladder neck position, and urethral mobility may all exert different effects on bladder wall thickness at the trigone, dome, or both. Urethral hypermobility may distort the urethral axis and perhaps may result in a thickened bladder wall. Alteration of the anatomic structures of the lower urinary tract may result in functional disorders and vice versa. When the urethra, which is the urinary conduit and controller of continence, malfunctions, it may cause urinary symptoms and may induce subsequent morphologic changes in the lower urinary tract. Anatomically, the bladder trigone and dome develop from different embryologic structures, and physiologically, they have different functions. 5 Therefore, changes in bladder wall thickness at either the trigone or dome may reflect different pathophysiologic mechanisms. The aim of this study was to explore the association between a thickened bladder wall at either the trigone or dome on ultrasonography and demographic, anatomic, and urodynamic variables. We postulated that different alterations in urethral function may cause different morphologic changes in the bladder wall. Materials and Methods We retrospectively reviewed the records of consecutive female patients who visited our urogynecologic clinic from August 1996 to August 2002. Those who had undergone a urodynamic study, ultrasonographic evaluation of the lower urinary tract, urinalysis, urine culture, or a combination thereof were identified. Records were excluded from the study if there was evidence of (1) hematuria, recurrent dysuria, abnormal urinalysis findings, or positive urine culture results; (2) a history of pelvic surgery, neuropathy (central or peripheral), diabetes mellitus, or radiation therapy; or (3) greater than 50 ml of residual urine on urodynamic studies, ultrasonographic studies, or both. 6 With the patient in a supine position and with a comfortably full bladder, transvaginal ultrasonographic cystourethrography was performed with a Toshiba SSA-260A scanner (Toshiba Medical Systems Co, Ltd, Tokyo, Japan) and a 5.0-MHz vaginal probe. The morphologic characteristics of the lower urinary tract were evaluated at rest and during a maximum Valsalva maneuver. Data recorded included the bladder neck position, development of bladder neck funneling, opening of the proximal urethra, and formation of a cystocele, prolapse, or herniation of the bladder base below the urethrovesical junction. 4 The images were frozen at rest and during the maximum Valsalva maneuver for measurement of the bladder neck position. Two lines were drawn on the frozen images, 1 from the lower border of the pubic symphysis to the bladder neck (internal urethral orifice) and the other denoting the midline of the pubic symphysis. The position of the bladder neck was quantified by measuring the angle between these 2 lines. The rotational angle was defined as the difference between the angles during resting and straining. After the bladder emptied, bladder wall thickness at the trigone and dome was measured at the thickest part, perpendicular to the luminal surface (Fig. 1). Urodynamic studies included spontaneous uroflowmetry, filling and voiding phase cystometry, and a urethral pressure profile during both resting and straining. Cystometry was performed at a filling rate of 80 ml/min with the patient seated upright in a birthing chair. The intravesical pressure was measured with a fluid-filled catheter (4.5F), and the intra-abdominal pressure was measured transrectally with a latex rectal catheter. A voiding study was carried out with the bladder filled to its maximum cystometric capacity, the patient in the seated position, and the catheters still in place. Static and stress urethral pressure profiles were obtained with the patient sitting at 45. Data were recorded continuously on a Medical Measurement Systems UD-2000 multichannel recorder (Medical Measurement Systems BV, Enschede, the Netherlands). The parameters examined for association with bladder wall thickness included age, gravidity, parity, menopausal status, bladder neck position at rest and during straining, urethral mobility (i.e., rotational angle of the bladder neck), and urodynamic variables on the pressure flow study and urethral pressure profile (Table 1). Associations between bladder wall thickness at either the dome or trigone and each examined parameter were summarized with the Pearson or Spearman rank correlation coefficient. Multivariate analysis was used to evaluate the 778 J Ultrasound Med 22:777 782, 2003

Yang and Huang influence of various parameters on bladder wall thickness. Analysis of variance was used to test for differences among multiple groups for continuous measured variables. Multiple comparisons were conducted with the Scheffé test if means varied significantly. To test the distribution of discrete variables, the χ 2 test was used. All analyses were conducted in SPSS 10.0 for Windows (SPSS Inc, Chicago, IL). P <.05 was considered significant. The terminology, definitions, and units conformed to the standards recommended by the International Continence Society, 7 except where specifically noted. Results The records of 492 patients were evaluated in this study. These included 248 patients with a diagnosis of urodynamic stress incontinence, 38 with detrusor overactivity (having a detrusor contraction in association with urgency, urinary leakage, or both during the filling phase of cystometry), 39 with mixed incontinence (having criteria for both urodynamic stress incontinence and detrusor overactivity), 35 with a hypersensitive bladder (having a volume at the first desire to void of Figure 1. Measurement of bladder wall thickness at the trigone (T) and dome (D). The margin of the anterior bladder wall is obscured by an acoustic shadow originating from the pubic symphysis (sp); cx indicates cervix; u, urethra; and Ut, uterine corpus. Table 1. Urodynamic and Anatomic Findings in 492 Female Patients With LUTS Variable Mean ± SE Range Urodynamic investigation Pressure flow study Maximum flow rate, ml/s 22.2 ± 1.2 4 67 Time to maximum flow, s 26.5 ± 2.3 1 284 P ves O 48.9 ± 0.9 9 88 P det O 25.8 ± 0.7 1 65 Micturition resistance O/(mL/s) 2 0.31 ± 0.05 0.01 18.75 Intravesical opening pressure O 50.2 ± 0.9 15 216 Detrusor opening pressure O 25.9 ± 0.7 1 113 Urethral pressure profile Functional profile length, mm 30.4 ± 0.45 11.0 35.0 Maximum urethral closure pressure O 71.0 ± 1.7 20 136 Length to maximum urethral pressure, mm 15.7 ± 0.9 3.0 30.8 AUC total O cm 158 ± 3 24 392 AUC proximal O cm 85 ± 2 11 226 Q 1, % 103 ± 1 1 287 Q 2, % 102 ± 1 1 200 Ultrasonographic evaluation Resting bladder neck angle, 97.8 ± 1.0 34 192 Straining bladder neck angle, 147.6 ±1.5 50 235 Rotational angle of the bladder neck, 50.2 ± 1.4 16 145 Bladder wall thickness at trigone, mm 5.8 ± 0.1 2.7 13.5 Bladder wall thickness at dome, mm 5.9 ± 0.1 2.8 13.0 AUC proximal indicates proximal area under the urethral pressure profile curve; AUC total, total area under the urethral pressure profile curve; P det, detrusor pressure at maximum flow; P ves, intravesical pressure at maximum flow; Q 1, pressure transmission ratio in the first quarter of the urethra; and Q 2, pressure transmission ratio in the second quarter of the urethra. J Ultrasound Med 22:777 782, 2003 779

Bladder Wall Thickness on Ultrasonographic Cystourethrography <100 ml and a maximum cystometric capacity of <300 ml), 8 42 with voiding difficulty (having a maximum flow rate of <15 ml/s for patients younger than 60 years or <10 ml/s for patients older than 60 years), 9 and 90 with normal findings from urodynamic studies. The mean age of the subjects was 48.1 years (range, 25 78 years); the mean gravidity was 4 (range, 0 15); and the mean parity was 2.9 (range, 0 8); 177 women (36%) were postmenopausal. The urodynamic results and ultrasonographic findings are shown in Table 1. Factors Affecting Bladder Wall Thickness Table 2 shows the correlation between bladder wall thickness and demographic, anatomic, and urodynamic variables by univariate and multivariate analyses. Bladder wall thicknesses at the trigone and dome correlated with each other. Age, resting bladder neck angle, urethral mobility, and maximum urethral closure pressure were associated with bladder wall thickness at both the trigone and dome. Urodynamically, thickness at the trigone was positively associated with pressure transmission ratios in the first and second quarters of the urethra; thickness at the dome was positively associated with intravesical pressure at maximum flow and with detrusor opening pressure. Age and intravesical pressure at maximum flow were independently associated with bladder wall thickness at the trigone and dome (r = 0.370; P =.007; and r = 0.316; P =.028), respectively. Bladder Wall Thickness in Different Urodynamic Groups As displayed in Figure 2, patients with a hypersensitive bladder had a significantly thinner bladder wall at the dome, trigone, or both than patients in the other diagnostic groups, except for those with mixed incontinence. Compared with all other patients, those with a hypersensitive bladder were significantly younger (mean age, 40.2 versus 48.6 years; P <.00001), had lower mean parity (2.1 versus 2.9; P =.0013), were less likely to be postmenopausal (20% versus 39%; P <.00001), had lower mean resting and straining bladder neck angles (87 versus 98 and 113 versus 148 ; P <.00001; P <.00001, respectively), and had a lower mean rotational angle of the bladder neck (26 versus 50 ; P <.00001). Discussion Less invasive measures for assessing female LUTS would be welcome additions to the urologic and urogynecologic fields. Currently, videocystourethrography is the criterion standard for urodynamic investigation because it simultaneously offers both urodynamic and anatomic assessment of the lower urinary tract. 10 However, it is not widely available because of its sophistication and concerns about radiation exposure. In addition, measuring bladder wall thickness on videocystourethrography is diffi- Table 2. Significant Associations Between Bladder Wall Thickness and Demographic, Anatomic, and Urodynamic Variables by Univariate and Multivariate Analyses Variable BWt BWd Age 1 * r = 0.356; SE = 0.047; P <.0001 r = 0.155; SE = 0.050; P =.002 Parity r = 0.302; SE = 0.049; P <.0001 NS Menopause r = 0.212; SE = 0.068; P =.002 NS RBN r = 0.132; SE = 0.046; P =.004 r = 0.107; SE = 0.046; P =.021 ROBN r = 0.119; SE = 0.046; P =.01 r = 0.156; SE = 0.046; P =.001 BWt 2 * r = 0.419; SE = 0.042; P <.0001 BWd 1 * r = 0.419; SE = 0.042; P <.0001 MUCP r = 0.277; SE = 0.115; P =.019 r = 0.370; SE = 0.111; P =.001 P ves 2 * NS r = 0.222; SE = 0.098; P =.027 P det.open NS r = 0.202; SE = 0.099; P =.046 Q 1 r = 0.201; SE = 0.053; P <.0001 NS Q 2 r = 0.169; SE = 0.054; P =.002 NS BWd indicates bladder wall thickness at the dome; BWt, bladder wall thickness at the trigone; MUCP, maximum urethral closure pressure; NS, not significant; P det.open, detrusor opening pressure; P ves, intravesical pressure at maximum flow; Q 1, pressure transmission ratio in the first quarter of the urethra; Q 2, pressure transmission ratio in the second quarter of the urethra; r, Pearson or Spearman rank correlation coefficient; RBN, resting bladder neck angle; ROBN, rotational angle of the bladder neck; and SE, SE of the slope. *The different superscript number indicates the independent factor for the bladder wall thickness at a specific site after multivariate analysis ( 1 for BWt and 2 for BWd). 780 J Ultrasound Med 22:777 782, 2003

Yang and Huang cult. Cystourethroscopy is another option for detecting bladder wall lesions, but it is an invasive procedure. 11 Transvaginal ultrasonography provides serial noninvasive examinations for assessing the condition of the bladder wall, which is why we find it a useful method for examining the lower urinary tract in women with LUTS. The normal bladder wall is 3 to 6 mm thick, 12 although it may vary with intravesical volume. It may be thickened secondary to chronic infection, inflammation after surgery, or radiation. A decrease in bladder wall thickness may suggest clearing of an infection or inflammation. 13,14 Because an infection may increase bladder wall thickness and may lead to detrusor overactivity, 15 we excluded patients with any evidence of infection or residual urine. In their study, Khullar et al 3 averaged the bladder wall thickness at the trigone, dome, and anterior bladder wall to develop criteria for detection of detrusor overactivity. This approach, however, fails to take into account the developmental and functional differences of the surpratrigonal and trigonal porions of the bladder. We did not measure the thickness of the anterior bladder wall in our study because of its imprecise image on ultrasonography. The anterior bladder wall is shaded by the acoustic shadow from the pubic symphysis, making measurement inaccurate. We assumed, too, that the supratrigonal portion of the bladder wall, if not affected by a local inflammatory lesion, may function with the dome as a single unit, so that measurement of the dome alone is sufficient. As stated in our previous report, 4 age, parity, menopause, resting bladder neck position, urethral mobility, and different urodynamic parameters have variable effects on thickness at the trigone or dome. Functionally, bladder wall thickness at different sites was associated with specific urodynamic variables. Increased detrusor opening pressure and intravesical pressure at maximum flow, indicating compressive urethral obstruction, 16 18 were correlated with a thickened bladder wall at the dome, and increased pressure transmission ratios in the first and second quarters of the urethra, signifying extraurethral compression, 19 were associated with increased thickness at the trigone. Anatomically, the bladder wall thickness was negatively associated with the resting bladder neck angle but was positively correlated with the rotational angle of Figure 2. Scatterplots of bladder wall thickness at the trigone and dome in different urodynamic diagnostic groups. Asterisks indicate significant mean differences when compared between the hypersensitive bladder group and other diagnostic groups by Scheffé test (P <.05); DO, detrusor overactivity; HB, hypersensitive bladder; MI, mixed incontinence; NE, normal findings on a urodynamic study; USI, urodynamic stress incontinence; and VD, voiding difficulty. the bladder neck. A high resting position and a greater rotational angle of the bladder neck imply urethral hypermobility, 4 which may distort the urethral axis and may result in a thickened wall at the dome. Urethral hypermobility is significantly associated with a cystocele, 4 pelvic organ prolapse, or both, which may exert external compression on the urethra 18 and may lead to a thickened wall at the trigone. A thickened bladder wall in different areas may denote specific pathophysiologic changes related to urethral obstruction. Urethral resistance, an index of constrictive urethral obstruction, was not correlated with bladder wall thickness in any diagnostic category in this study group. Unlike Khullar et al, 3 we did not find that women with detrusor overactivity had an appreciably thicker bladder wall than those in other diagnostic groups. In this study, a thickened bladder wall was a common finding in female patients with LUTS except in those with a hypersensitive bladder. Younger age, lower parity, premenopausal status, and a smaller rotational angle of the bladder neck are characteristics of women with a hypersensitive bladder and are responsible for the thinner bladder wall. Overall, this study shows that the bladder wall may be thickened when different pathologic entities are present in the bladder. Although dif- J Ultrasound Med 22:777 782, 2003 781

Bladder Wall Thickness on Ultrasonographic Cystourethrography ferentiation of various urodynamic diagnoses simply on the basis of bladder wall thickness seems impossible, in combination with the association between the thickness and urodynamic variables, bladder wall thickness may be helpful for detecting differences in thickness in patients treated for urinary problems and for monitoring changes over time. Verification of its clinical significance, however, will be the subject of another study. In conclusion, our findings indicate that the pathogenesis of a thickened bladder wall is multifactorial and that thickening at the trigone or dome may imply different urodynamic changes. References 1. Petri E, Koelbl H, Schaer G. What is the place of ultrasound in urogynecology? A written panel. Int Urogynecol J Pelvic Floor Dysfunct 1999; 10:262 273. 2. Schaer GN, Perucchini D, Munz E, Peschers U, Koechli OR, Delancey JO. Sonographic evaluation of the bladder neck in continent and stress-incontinent women. Obstet Gynecol 1999; 93:412 416. 3. Khullar V, Cardozo LD, Salvatore S, Hill S. Ultrasound: a noninvasive screening test for detrusor instability. Br J Obstet Gynaecol 1996; 103:904 908. 4. Yang JM, Huang WC. Discrimination of bladder disorders in female lower urinary tract symptoms on ultrasonographic cystourethrography. J Ultrasound Med 2002; 21:1249 1255. 5. Walters MD. Anatomy of the lower urinary tract and pelvic floor. In: Walters MD, Karram MM (eds). Clinical Urogynecology. St Louis, MO: CV Mosby Co; 1993:3 16. 6. Haylen BT, Frazer MI, MacDonald JH. Assessing the effectiveness of different urinary catheters in emptying the bladder: an application of transvaginal ultrasound. Br J Urol 1989; 64:353 356. 8. Ramsay IN, Ali HM, Hunter M, Stark D, Donaldson K. A randomized controlled trial of urodynamic investigation prior to conservative treatment of urinary incontinence in the female. Int Urogynecol J Pelvic Floor Dysfunct 1995; 6:277 281. 9. Stanton SL, Ozsoy C, Hilton P. Voiding difficulties in the female: prevalence, clinical and urodynamic review. Obstet Gynecol 1983; 61:144 147. 10. McLellan A, Cardozo L. Urodynamic techniques. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12:266 270. 11. Cundiff GW, Bent AE. The contribution of urethrocystoscopy to evaluation of lower urinary tract dysfunction in women. Int Urogynecol J Pelvic Floor Dysfunct 1996; 7:307 311. 12. Chang TS, Bohm-Velez M, Mendelson EB. Nongynecologic applications of transvaginal sonography. AJR Am J Roentgenol 1993; 160:87 93. 13. Hung WC, Yang JM. Transvaginal sonography in the treatment of a rare case of total urethral stenosis with a vesicovaginal fistula. J Ultrasound Med 2002; 21:463 467. 14. Yang JM, Su TH, Wang KG. Transvaginal sonographic findings in vesicovaginal fistula. J Clin Ultrasound 1994; 22:201 203. 15. Moore KH, Simons A, Mukerjee C, Lynch W. The relative incidence of detrusor instability and bacterial cystitis detected on the urodynamic-test day. BJU Int 2000; 85:786 792. 16. Yang JM, Huang WC. Implications of abdominal straining in women with lower urinary tract symptoms. Urology 2002; 60:428 433. 17. Griffiths DJ. Pressure-flow studies of micturition. Urol Clin North Am 1996; 23:179 297. 18. Carr LK, Webster GD. Bladder outlet obstruction in women. Urol Clin North Am 1996; 23:385 391. 19. Bump RC, Fantl JA, Hurt WG. The mechanism of urinary continence in women with severe uterovaginal prolapse: results of barrier studies. Obstet Gynecol 1988; 72:291 295. 7. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower urinary tract function: report from the standardization subcommittee of the International Continence Society. Neurourol Urodyn 2002; 21:167 178. 782 J Ultrasound Med 22:777 782, 2003